![](https://www.kindai.ac.jp/data/images/professor/811.jpg)
ZAIMA Nobuhiro
Department of Applied Biological Chemistry | Professor |
Last Updated :2024/08/31
■Researcher comments
List of press-related appearances
1
■Researcher basic information
J-Global ID
Research Keyword
- 脂質代謝異常 質量分析イメージング 質量顕微鏡 脂質蓄積ミオパチー 脂質 ATGL変異症 脂肪肝 動脈硬化 病理解析 粥状動脈硬化 腹部大動脈瘤 自閉症
■Career
Career
- 2020/04 - Today Kindai UniversityFaculty of Agriculture教授
- 2018 - Today 近畿大学アグリ技術革新研究所学際生命科学研究室
- 2015/04 - 2020/03 Kindai UniversityFaculty of Agriculture准教授
- 2016/09 - 2017/02 Imperial College Londonvisiting researcher
- 2011/04 - 2015/03 近畿大学農学部講師
- 2008/10 - 2011/03 Hamamatsu University School of Medicine分子イメージング先端研究センター特任助教
- 2007/04 - 2008/09 三菱化学生命科学研究所特別研究員
Educational Background
Member History
■Research activity information
Award
- 2024/05 日本栄養・食糧学会 令和6年度 日本栄養・食糧学会トピックス賞
- 2020 15th J. Oleo Sci. Impact Award
- 2018 日本栄養・食糧学会 奨励賞
受賞者: 財満信宏 - 2017 日本油化学会 第16回日本油化学会オレオサイエンス賞
受賞者: 財満信宏 - 2012 日本農芸化学会 日本農芸化学会2012年度大会トピックス賞
受賞者: 財満信宏 - 2011 日本農芸化学会 日本農芸化学会2011年度大会トピックス賞
受賞者: 財満信宏 - 2011 6th J.Oleo Sci. Impact Award
受賞者: 財満信宏 - 2010 J.Oleo Sci. Editors’ Award
受賞者: 財満信宏 - 2009 JOCS-ILSI JOCS-ILSI Japan Joint Symposium優秀ポスター賞
受賞者: 財満信宏 - 2009 日本油化学会 ヤングフェロー賞
受賞者: 財満信宏
Paper
- Mayo Higashihara; Hirofumi Enomoto; Tomoko Sumi; Tatsuya Moriyama; Nobuhiro ZaimaJournal of oleo science 73 (6) 895 - 903 2024/06 [Refereed]
Abdominal aortic aneurysm (AAA) is a vascular disease characterized by progressive dilation of the abdominal aorta. Previous studies have suggested that dietary components are closely associated with AAA. Among those dietary components, eicosapentaenoic acid (EPA) is considered to have suppressive effects on AAA. In the AAA wall of AAA model animals bred under EPA-rich condition, the distribution of EPA-containing phosphatidylcholine (EPA-PC) has been reported to be similar to that of the markers of mesenchymal stem cells (MSCs) and M2 macrophages. These data suggest that the suppressive effects of EPA on AAA are related to preferential distribution of specific cells in the aortic wall. However, the distribution of EPA-PC in the AAA wall of AAA model animals fed a diet containing small amounts of EPA, which has not been reported to inhibit AAA, has not yet been explored. In the present study, we visualized the distribution of EPA-PCs in the AAA wall of AAA model animals fed a diet containing small amounts of EPA (1.5% EPA in the fatty acid composition) to elucidate the vasoprotective effects of EPA. Positive areas for markers of MSCs were significantly higher in the region where EPA-PC was abundant compared to the regions where EPA-PC was weakly detected, but not for markers of M2 macrophages, matrix metalloproteinase (MMP)-2, and MMP-9. The distribution of MSC markers was similar to that of EPA-PC but not that of M2 macrophages and MMPs. These data suggest preferential incorporation of EPA into MSCs under the conditions used in this study. The incorporation of EPA into certain cells may differ according to dietary conditions, which affect the development of AAA. - Hirona Kugo; Tatsuya Moriyama; Nobuhiro ZaimaBiotechnic & histochemistry : official publication of the Biological Stain Commission 1 - 7 2024/05 [Refereed]
Abdominal aortic aneurysm (AAA) is a vascular disease that involves aortic wall dilation. Cigarette smoking is an established risk factor and rupture, and nicotine may be a major contributor to the onset of AAA. In humans the condition is associated with stenosis of the vasa vasorum (VV), which may be caused by nicotine. In this study, we evaluated the effects of nicotine on VV pathology. After 4 weeks of nicotine administration to rats using an osmotic pump, the VV patency rate in the nicotine administration group was significantly lower than that in the control group. The levels of Ki-67, a cell proliferation marker, were significantly increased in the regions containing VV in the nicotine group, as were hypoxia inducible factor-α levels. Collagen levels around VV were significantly lower in the nicotine group than in the controls. Our data suggest that nicotine can cause VV stenosis by inducing abnormal proliferation of smooth muscle cells in the VV. The increased risk of AAA development due to cigarette smoking may be partially explained by nicotine-induced VV denaturation and collagen fiber degradation. - Mayo Higashihara; Hirona Kugo; Tomomi Nakamura; Tomoko Sumi; Daisuke Shimizu; Keisuke Kiriyama; Mica Fujita; Keita Sutoh; Tatsuya Moriyama; Nobuhiro ZaimaPharmaNutrition Elsevier BV 100360 - 100360 2213-4344 2023/10 [Refereed]
- Hirona Kugo; Yuki Sugiura; Rena Fujishima; Shintou Jo; Hirotaka Mishima; Erina Sugamoto; Hiroki Tanaka; Satoshi Yamaguchi; Yoshihiko Ikeda; Ken-Ichi Hirano; Tatsuya Moriyama; Nobuhiro ZaimaBiomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 160 114299 - 114299 2023/01 [Refereed]
Medical therapeutic options to prevent rupture of abdominal aortic aneurysm (AAA), a critical event, must be developed. Moreover, further understanding of the process of AAA development and rupture is crucial. Previous studies have revealed that aortic hypoperfusion can induce the development of AAA, and we successfully developed a hypoperfusion-induced AAA animal model. In this study, we examined the effects of medium-chain triglycerides (MCTs), tricaprylin (C8-TG) and tricaprin (C10-TG), on hypoperfusion-induced AAA rat model. We estimated the effects of MCTs on aortic pathologies, mechanical properties of the aorta, and development of AAA. C10-TG, but not C8-TG, significantly suppressed AAA development and completely prevented the rupture. We observed that C10-TG prevented the development and rupture of AAA, but not C8-TG. Additionally, regression of AAA diameter was observed in the C10-TG group. Pathological analysis revealed C10-TG improved the hypoperfusion-induced increase in hypoxia-inducible factor-1α levels, medial smooth muscle cells (SMCs) loss, degeneration of aortic elastin and collagen fibers, and loss of aortic wall elasticity. In addition, regression of the formed AAA was observed by administration of C10-TG after AAA formation. C10-TG administration after AAA formation improved degeneration of AAA wall including degradation of aortic elastin and collagen fibers, stenosis of vasa vasorum, and loss of medial SMCs. These data suggest C10-TG can prevent AAA by attenuating aortic hypoperfusion and degeneration. Considering the clinical safety of C10-TG, C10-TG can be a promising AAA drug candidate. - Hirofumi Enomoto; Nobuhiro ZaimaJournal of chromatography. B, Analytical technologies in the biomedical and life sciences 1216 123601 - 123601 2023/01 [Refereed]
Carnitine is essential for energy production and lipid metabolism in skeletal muscle. Carnosine and its methylated analogs anserine and balenine are histidine-containing imidazole dipeptides, which are antioxidative compounds. They are major health-related components in meat; however, analytical technique to investigate their distribution among tissues have not fully established. Here, we performed desorption electrospray ionization (DESI)-mass spectrometry imaging (MSI) of pork chop sections containing longissimus thoracis et lumborum muscle (loin), intermuscular fat tissue, transparent tissue, and spinalis muscle to investigate the distributions of carnitine and imidazole dipeptides. Liquid chromatography-MS revealed that the concentrations of carnitine, carnosine, anserine, and balenine were 11.0 ± 0.9, 330.1 ± 15.5, 21.2 ± 1.5, and 9.6 ± 0.5 mg/100 g, respectively. In the mass spectrum obtained by DESI-MSI, peaks corresponding to the chemical formulae of carnitine and imidazole dipeptides were detected. DESI-MSI provided definite identification of carnitine, while DESI-tandem MSI (MS/MSI) was necessary to accurately visualize carnosine, anserine, and balenine. Carnitine and these imidazole dipeptides were mainly distributed in the loin and spinalis muscle, while their distribution was not uniform in both muscle tissues. In addition, the balance between both tissues were different. The concentration of carnitine was higher in the spinalis muscle than that in the loin, while those of imidazole dipeptides were higher in the loin than those in the spinalis muscle. These results were consistent with those obtained by liquid chromatography-MS quantification, suggest that DESI-MSI analysis is useful for the distribution analysis of carnitine and imidazole dipeptides in meat. - Hirona Kugo; Tatsuro Yata; Rie Kanai; Ena Naruse; Kazunori Inuzuka; Hiroki Tanaka; Kenichi Yanagimoto; Tatsuya Moriyama; Naoki Unno; Miho Kogirima; Nobuhiro ZaimaJournal of oleo science 72 (2) 211 - 218 2023/01 [Refereed]
Abdominal aortic aneurysm (AAA) is a vascular disease that involves asymptomatic progressive expansion of the abdominal aorta. Aneurysm rupture is associated with a high mortality rate. Dietary conditions may be associated with the development and rupture of AAA. However, the relationship between nutrition and AAA is not completely understood. In this study, a nutrition survey was conducted using a brief self-administered diet history questionnaire (BDHQ) to evaluate the relationship between AAA and dietary habits. One-hundred and twenty-six Japanese people participated in the nutrition survey. Food intake status was analyzed in four groups: the analyzed group-1 (all men), analyzed group-2 (men with smoking history), analyzed group-3 (all women) and analyzed group-4 (women without smoking history). In group-2 and group-3, the intake of citrus fruits was significantly lower in the AAA group than in the non-AAA group. In group-2, the intake of soybean and soybean products was significantly lower in the AAA group than in the non-AAA group. In analyzed group-3, the intake of other vegetables (vegetables except for green and yellow vegetables and soybeans) and seafood was significantly lower in the AAA group than in the non-AAA group. This study suggests that AAA onset may be associated with low intake of fruits, soybeans, vegetables, and seafood. - Rikiya Shimada; Erika Yano; Nobuhiro Zaima; Tatsuya MoriyamaFood Science and Technology Research Japanese Society for Food Science and Technology 29 (6) 553 - 558 1344-6606 2023
- Kazuya Yamada; Kohei Toyota; Yamato Tsunoda; Yoshiharu Matahira; Shinichi Matsumura; Yuri Yoshioka; Nobuhiro Zaima; Naoki UnnoExperimental and therapeutic medicine 25 (1) 57 - 57 2023/01 [Refereed]
Approximately 1.14 billion smokers worldwide are at risk of developing tumors, cardiovascular diseases and respiratory diseases. Smoking cessation is the first choice of health care; however, the disease should be attenuated in individuals who never stop smoking, which escalates medical costs. Therefore, alternative options are needed to manage the social burden. The present study proposed an alternative method to prevent such diseases by inhalation of β-caryophyllene (BCP). A placebo-targeted, dose-searching, double-blind, parallel-group comparative study was conducted on 19 subjects. The BCP intervention was performed using a flavor capsule inserted in a cigarette filter. The primary endpoint was the reducibility of brachial-ankle pulse wave velocity (baPWV). The secondary endpoints were confirmation of the bioavailability of BCP inhalation with cigarette smoke, confirmation of the effect of BCP inhalation on respiratory function, and association between respiratory function and blood concentration and baPWV reduction. The BCP concentration in the blood reached 4 ng/ml in the BCP 15% group 10 min after inhalation. The baPWV decreased in BCP-inhaling subjects whose initial baPWV was >1,300 cm/sec. The correlation analyses revealed that the higher the forced expiratory volume in 1 sec, the better the transition of baPWV. Inhaled BCP with cigarette smoke could reduce the baPWV and the risk of cardiovascular diseases in smokers. These findings indicated that with the introduction of BCP capsule-cigarettes in the future, smokers will be able to take care of their health, which may help reduce national medical costs. BCP microcapsules placed in cigarette wrapping paper may possibly reduce the risk of sidestream smoke and contribute to improved public health. This clinical research was retrospectively registered in the University Hospital Medical Information Network (UMIN)-Clinical Trials Registry with the following identifications: UMIN000048510 and UMIN000048512 on August 15, 2022. - Hirotaka Noda; Chikao Yutani; Nobuhiro Zaima; Sei Komatsu; Nobuzo Iwa; Satoru Takahashi; Mitsuhiko Takewa; Tomoki Ohara; Kazuhisa KodamaJournal of cardiology cases 26 (5) 364 - 366 2022/11 [Refereed]
UNLABELLED: We visualized macrophages engulfing cholesterol crystals from spontaneously ruptured aortic plaques sampled by angioscopy. Docosahexaenoic acid cholesterol ester (DHA-CE) was demonstrated by imaging mass spectrometry. DHA-CE is reported to be produced by macrophages against inflammation. Activities of macrophages against atherosclerosis inside plaques was shown from spontaneously ruptured aortic plaques in situ. LEARNING OBJECTIVES: Activities of macrophages such as engulfing cholesterol crystals and producing docosahexaenoic acid cholesterol ester were shown from spontaneously ruptured aortic plaques in situ. - Chihiro Kishi; Mayo Higashihara; Yuki Takemoto; Moeka Kamei; Yuri Yoshioka; Shinichi Matsumura; Kazuya Yamada; Takanori Kobayashi; Yoshiharu Matahira; Tatsuya Moriyama; Nobuhiro ZaimaBiomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 153 113423 - 113423 2022/09 [Refereed]
β-caryophyllene (BCP) is a volatile bicyclic sesquiterpenoid found in essential oils obtained from several spices such as black pepper, oregano, basil, rosemary, cinnamon, and clove. BCP is a selective agonist of cannabinoid receptor 2 (CB2 receptor), and orally administered BCP exhibits various biological activities, including anti-inflammatory, antioxidant, and neuroprotective effects. However, it is still unclear how volatile BCP affects living organisms. We previously reported that inhaled BCP is transferred to sera and organs in mice; additionally, metabolomic analysis revealed inhaled BCP affect the dynamics of metabolites in the livers of mice. These data suggest that inhaled BCP may affect several biological activities by stimulating biological systems. In this study, we evaluated the effects of BCP inhalation on nicotine-induced degeneration of the aortic wall. In the group of mice which inhaled volatile BCP, nicotine-induced increases in elastic fiber degradation and matrix metalloproteinase-2 (MMP-2)-positive areas were attenuated. In addition, BCP improved the nicotine-induced stiffness of aortae and vulnerability to aortic rupture. In cultured aortae, the suppressive effects of BCP were inhibited by the CB2 receptor inhibitor AM630. These results suggest that inhaled BCP is incorporated into the aortic wall and prevents nicotine-induced degeneration of the aorta via a CB2 receptor-dependent pathway. - Atsushi Kurata; Shogo Kiyohara; Tomoya Imai; Shino Yamasaki-Yashiki; Nobuhiro Zaima; Tatsuya Moriyama; Noriaki Kishimoto; Koichi UegakiScientific reports 12 (1) 13330 - 13330 2022/08 [Refereed]
We investigated the characteristics and functionalities of extracellular vesicles (EVs) from Lactiplantibacillus plantarum (previously Lactobacillus plantarum) towards host immune cells. L. plantarum produces EVs that have a cytoplasmic membrane and contain cytoplasmic metabolites, membrane and cytoplasmic proteins, and small RNAs, but not bacterial cell wall components, namely, lipoteichoic acid and peptidoglycan. In the presence of L. plantarum EVs, Raw264 cells inducibly produced the pro-inflammatory cytokines IL-1β and IL-6, the anti-inflammatory cytokine IL-10, and IF-γ and IL-12, which are involved in the differentiation of naive T-helper cells into T-helper type 1 cells. IgA was produced by PP cells following the addition of EVs. Therefore, L. plantarum EVs activated innate and acquired immune responses. L. plantarum EVs are recognized by Toll-like receptor 2 (TLR2), which activates NF-κB, but not by other TLRs or NOD-like receptors. N-acylated peptides from lipoprotein19180 (Lp19180) in L. plantarum EVs were identified as novel TLR2 ligands. Therefore, L. plantarum induces an immunostimulation though the TLR2 recognition of the N-acylated amino acid moiety of Lp19180 in EVs. Additionally, we detected a large amount of EVs in the rat gastrointestinal tract for the first time, suggesting that EVs released by probiotics function as a modulator of intestinal immunity. - Hirona Kugo; Hirofumi Enomoto; Kenichi Yanagimoto; Hiroki Tanaka; Tatsuya Moriyama; Nobuhiro ZaimaFood & function 13 (14) 7540 - 7547 2022/07 [Refereed]
Abdominal aortic aneurysm (AAA) is a vascular disease characterized by progressive dilation of the aorta which is reportedly associated with inflammation. Previous studies suggested that eicosapentaenoic acid (EPA) has suppressive effects on AAA development via anti-inflammatory activities. However, relationships between the anti-inflammatory effects and the cells in the AAA wall are poorly understood. In this study, we visualized the distribution of EPA-containing phosphatidylcholine (EPA-PC) in the AAA wall. EPA-PC was not ubiquitously distributed in both animal (hypoperfusion-induced AAA model) and human AAA walls, suggesting the preferential incorporation of EPA into certain cells. In the EPA-PC-high region of both animal and human AAAs, mesenchymal stem cell (MSC) marker positive areas were significantly higher than those in the EPA-PC-low region. Matrix metalloproteinase-positive MSCs were significantly lower in the AAA wall of the animal model which was administered EPA-rich fish oil. These data suggest that EPA is associated with the attenuation of MSC dysfunctions, which result in the suppression of AAA development. - Yuki Takemoto; Chihiro Kishi; Hinano Ehira; Nobutaka Matsui; Taichi Yamaguchi; Yuri Yoshioka; Shinichi Matsumura; Tatsuya Moriyama; Nobuhiro ZaimaScientific reports 12 (1) 11039 - 11039 2022/06 [Refereed]
Turmerones (α-turmerone, β-turmerone, and ar-turmerone) are the major volatile compounds in turmeric (Curcuma longa), a perennial herb of the ginger family. We previously reported that inhaled volatile turmerones could be transferred in the blood and organs. However, the difference between the two pathways, oral administration and inhalation, and the effect of inhaled turmerones on biological activities remain unknown. In this study, we compared the distribution patterns of turmerones after oral administration and inhalation. The relative levels (concentrations of turmerones in each organ/serum) in the lung, olfactory bulb, brain, heart, kidney, and epididymal fat in the inhalation group tended to be, or are significantly, higher than in the oral administration group. The relative levels of brown adipose tissue in the inhalation group were lower than in the oral administration group. Long-term (50 days) inhalation to volatile turmerones suppressed weight gain and hypertrophy of adipocytes in the epididymal fat of mice fed a high-fat diet. These results suggest that inhaled turmerones can be incorporated into the organs of mice via different pathway from as to those from oral administration and can affect the biological function of the organs under certain conditions. - Kento Miyamoto; Sakura Hasuike; Hirona Kugo; Wanida Sukketsiri; Tatsuya Moriyama; Nobuhiro ZaimaJournal of oleo science 71 (6) 889 - 896 2022/06 [Refereed]
Women are more resistant to vascular diseases; however, the resistance is reduced after menopause. It has been reported that the risk of vascular diseases such as atherosclerosis and abdominal aortic aneurysm is increased in postmenopausal women. Currently, methods to prevent vascular disease in postmenopausal women have not been established. Isoflavones are promising functional food factors that have a chemical structure similar to estrogen. In this study, we investigated the effects of isoflavones on ovariectomized (OVX)-induced degeneration of the aortic wall in mice. Increased destruction of elastic fibers in the thoracic and abdominal aorta was observed in the OVX group, and isoflavones attenuated the destruction of elastic fibers. The positive areas of matrix metalloproteinase (MMP)-2 and MMP-9 in the OVX group were higher than those in the control group. Isoflavones decreased the positive areas of MMP-2 and MMP-9 compared to those in the OVX group. These data suggest that isoflavones have a suppressive effect on OVX-induced degeneration of the aortic wall by inhibiting the increase in MMP-2 and MMP-9. - Eri Izumi; Nana Tanahashi; Serina Kinugasa; Shota Hidaka; Nobuhiro Zaima; Tatsuya MoriyamaInternational journal of molecular sciences 23 (7) 2022/04Transdermal sensitization to allergens is of great concern as a sensitization route for food allergies. This skin-mediated invasion and sensitization to allergens is involved in skin barrier breakdown and inflammation, followed by the production of several kinds of cytokines. Cytokines such as thymic stromal lymphopoietin and thymus and activation-regulated chemokine are also involved. In this study, we investigated the suppressive effect of tannic acid (TA) on transdermal sensitization using ovalbumin (OVA), a major egg-white allergen. We also analyzed the mechanisms associated with the inhibitory effects of TA. The results showed that the co-application with TA prevents transdermal sensitization to OVA. As possible mechanisms, its anti-inflammatory and astringent effect on the skin and binding ability with the protein were considered. These results indicate that TA could be applied to cosmetics and lotions, which could suppress the transdermal sensitization to allergens.
- Hirona Kugo; Hiroki Tanaka; Tatsuya Moriyama; Nobuhiro ZaimaJournal of lipid research 63 (8) 100200 - 100200 2022/03 [Refereed]
- Mayo Higashihara; Rena Fujishima; Hirona Kugo; Tatsuya Moriyama; Nobuhiro ZaimaJournal of nutritional science and vitaminology 68 (Supplement) S143-S145 2022 [Invited]
Dietary habit is closely associated with healthspan. Functional food factors are key to maintaining a health metabolism in our bodies. Because functional food factors are main components to determine the quality of foods, many technologies have been established to analyze functional factors in foods. High-performance liquid chromatography-mass spectrometry or gas chromatography-mass spectrometry is a solid approach to detect functional food factors with high sensitivity and specificity. Findings obtained from these mass spectrometric approaches play essential roles in estimating the quality of foods. However, these technologies are not available for the analysis of the spatial distribution of molecules of interest in foods. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is considered an ideal approach to visualize distribution of molecules in foods. MALDI-MSI is a two-dimensional MALDI-MS technology that can detect compounds in a tissue section without purification, separation, or labeling. MALDI-MSI can be used to visualize the spatial distribution of wide range of food components including protein, peptides, amino acids, lipids, carbohydrate, and vitamins. Although the methodology of MALDI-MSI in food science is not yet fully established, the versatility of MALDI-MSI is expected to open a new frontier in food science. In this mini review, we briefly summarized the applications of MALDI-MSI in the field of food science. - Ayano Fukuzumi; Naoki Tokumasu; Ayato Matsuo; Erika Yano; Nobuhiro Zaima; Tatsuya MoriyamaAllergies 2021/12
- Tsukasa Sasoh; Hirona Kugo; Yuya Kondo; Kento Miyamoto; Momoka Minami; Mayo Higashihara; Hirokazu Kawamoto; Fumiaki Takeshita; Tatsuya Moriyama; Nobuhiro ZaimaAdipocyte 10 (1) 412 - 423 2021/12 [Refereed]
Vascular diseases such as atherosclerosis and aneurysms are associated with diet. Perivascular adipose tissue (PVAT) was reportedly involved in the regulation of vascular functions. It is suggested that imbalanced diets can cause PVAT inflammation and dysfunction as well as impaired vascular function. However, the association between diets and PVAT are not clearly understood. Here, we showed that a high-fat and a high-sucrose diet affected PVAT at different sites. A high-fat diet induced increased number of large-sized lipid droplets and increased CD (Cluster of differentiation) 68+ macrophage- and monocyte chemotactic protein (MCP)-1-positive areas in the abdominal aortic PVAT (aPVAT). In addition, a high-fat diet caused decreased collagen fibre-positive area and increased CD68+ macrophage- and MCP-1-positive areas in the abdominal aorta. In contrast, a high-sucrose diet induced increased number of large-sized lipid droplets, increased CD68+ macrophage- and MCP-1-positive areas, and decreased UCP-1 positive area in the thoracic aortic PVAT (tPVAT). A high-sucrose diet caused decreased collagen fibre-positive area and increased CD68+ macrophage- and MCP-1-positive areas in the thoracic aorta. These results could be attributed to the different adipocyte populations in the tPVAT and aPVAT. Our results provide pathological evidence to improve our understanding of the relationship between diet and vascular diseases. - Hirona Kugo; Wanida Sukketsiri; Kazuko Iwamoto; Satoki Suihara; Tatsuya Moriyama; Nobuhiro ZaimaAdipocyte 10 (1) 232 - 241 2021/12 [Refereed]
Abdominal aortic aneurysm (AAA) involves the degradation of vascular fibres, and dilation and rupture of the abdominal aorta. Hypoperfusion in the vascular walls due to stenosis of the vasa vasorum is reportedly a cause of AAA onset and involves the induction of adventitial ectopic adipocytes. Recent studies have reported that ectopic adipocytes are associated with AAA rupture in both human and hypoperfusion-induced animal models, highlighting the pathological importance of hypoperfusion and adipocytes in AAA. However, the relationship between hypoperfusion and AAA remains unknown. In this study, we investigated the changes in inflammation-related factors in adipocytes at low glucose and serum levels. Low glucose and serum levels enhanced the production of AAA-related factors in 3T3-L1 cells. Low glucose and serum levels increased the activation of protein kinase B (also known as Akt), extracellular signal-regulated protein kinase 1/2, p38, c-Jun N-terminal kinase, and nuclear factor (NF) кB at the protein level. The inflammatory factors and related signalling pathways were markedly decreased following the return of the cells to normal culture conditions. These data suggest that low glucose and serum levels increase the levels of inflammatory factors through the activation of Akt, mitogen activated protein kinase, and NF-κB signalling pathways. - Tomomi Nakamura; Kento Miyamoto; Hirona Kugo; Keita Sutoh; Keisuke Kiriyama; Tatsuya Moriyama; Nobuhiro ZaimaJournal of oleo science 70 (11) 1651 - 1659 2021/10 [Refereed]
Women are more resistant than men to the development of vascular diseases. However, menopause is a factor leading to deterioration of female vascular integrity, and it is reported that the risk of vascular diseases such as atherosclerosis and abdominal aortic aneurysm is increased in postmenopausal women. Although it is suggested that perivascular adipose tissue (PVAT) is deeply involved in the increased risk of vascular disease development, the effect of menopause on PVAT integrity is unknown. In this study, we aimed to elucidate the effect of menopause on PVAT in ovariectomized (OVX) rats. PVAT was divided into 4 regions based on characteristics. Hypertrophy and increased inflammation of adipocytes in the PVAT were observed in the OVX group, but the effects of OVX were different for each region. OVX induced matrix metalloproteinase (MMP) -9 which degrade extracellular matrix such as elastin and collagen fibers in PVAT. Degeneration of the arterial fibers of the thoracic and abdominal aorta were observed in the OVX group. These results indicate that OVX can cause dysfunction of PVAT which can cause degradation of arterial fibers. Appropriate management of PVAT may play an important role in the prevention and treatment of diseases originating from ovarian hypofunction. - Yuri Yoshioka; Shinichi Matsumura; Masanori Morimoto; Yuki Takemoto; Chihiro Kishi; Tatsuya Moriyama; Nobuhiro ZaimaJournal of agricultural and food chemistry 69 (35) 10163 - 10173 2021/09 [Refereed]
Alzheimer's disease (AD) is the most common neurodegenerative disease. Garlic reportedly has various physiological effects, including a role in protecting against dementia. However, the action mechanisms of garlic on AD are not entirely clear. In this study, we investigated the inhibitory activity of garlic essential oil (GEO) against AD-related enzymes and evaluated the distribution of active substances in GEO to the brain. We found that several sulfur compounds in GEO significantly inhibited AD-related enzymes. Sulfur compounds were detected in the serum and brain 6 h post administration. The ratios of allyl mercaptan (24.0 ± 3.9%) and allyl methyl sulfide (49.8 ± 15.6%) in the brain were significantly higher than those in GEO, while those of dimethyl trisulfide (0.89 ± 34.8%), allyl methyl trisulfide (0.41 ± 19.0%), and diallyl trisulfide (0.43 ± 72.8%) in the brain were significantly lower than those in GEO. Similar results were observed in the serum, suggesting that the organosulfur compounds were converted to allyl mercaptan or allyl methyl sulfide in the body. Although allyl mercaptan and allyl methyl sulfide are not the main components of GEO, they might be key molecules to understand the bioactivities of GEO in the body. - Ayana Ieda; Maki Wada; Yuuki Moriyasu; Yuuko Okuno; Nobuhiro Zaima; Tatsuya MoriyamaMolecules (Basel, Switzerland) 26 (13) 2021/06The effect of ellagic acid (EA), a naturally occurring polyphenolic compound, on the secretion of apolipoproteins from human hepatocytes, HepG2, was investigated. The levels of apoB and apoA-1 secreted in the cell culture medium were determined by sandwich ELISA. EA did not affect cell viability at the tested concentrations (up to 50 µM). EA suppressed the secretion of apoB and enhanced that of apoA-1 from HepG2 cells. However, cellular apoB levels were increased, suggesting that EA inhibited the trafficking of apoB during the process of secretion. In contrast, the increase in the cellular levels of apoA-1 was consistent with its secreted levels. These results indicate that EA inhibits the secretion of apoB from hepatocytes and increases the secretion of apoA-1. Both of these effects are beneficial for lipoprotein metabolism in the prevention of lifestyle-related diseases. The detailed mechanism underlying these effects of EA on lipoprotein metabolism should be elucidated in the future, but this naturally occurring polyphenolic compound might be antihyperlipidemic. Based on these results, EA is suggested as a candidate food-derived compound for the prevention of hyperlipidemia.
- Rena Fujishima; Hirona Kugo; Kenichi Yanagimoto; Hirofumi Enomoto; Tatsuya Moriyama; Nobuhiro ZaimaFood & function 12 (8) 3469 - 3475 2021/04 [Refereed]
Abdominal aortic aneurysm (AAA) is an aortic disease in which the aortic diameter is ≥3.0 cm; if left untreated, the aortic wall continues to weaken, resulting in progressive dilatation. Effective therapeutic drugs for AAA patients have not been discovered. Eicosapentaenoic acid (EPA) reportedly attenuates the development of AAA in experimental AAA animal models. However, the underlying mechanism of action is still not totally clear. To understand the mechanism, we visualized the distribution of EPA-containing phosphatidylcholine (PC) in the AAA wall by matrix-assisted laser desorption ionization-mass spectrometry imaging. EPA-containing PC was characteristically distributed in the AAA wall, and the positive area for the M2 macrophage marker was significantly higher in the region where EPA-containing PC was highly detected (region 2) than in the region where EPA-containing PC was poorly detected (region 1). The M1 macrophage marker levels were not different between regions 1 and 2. A comparative observation showed a similar distribution of the M2 macrophage marker and EPA-containing PC. These data suggest the preferential incorporation of EPA into M2 macrophages. Positive areas for matrix metalloproteinase 2 and malondialdehyde in region 2 were significantly lower than those in region 1. The reported suppressive effect of EPA on the development of AAA may be partly attributed to the increased anti-inflammatory property of M2 macrophages. - Yuuki Moriyasu; Chiho Fukumoto; Maki Wada; Erika Yano; Hiroshi Murase; Masatoshi Mizuno; Nobuhiro Zaima; Tatsuya MoriyamaFoods (Basel, Switzerland) 10 (4) 2021/04In this study, we fed obese model mice black soybean seed coat powder (BSCP) and evaluated the antiobesity effects. As a control, normal yellow soybean seed coat powder (YSCP) was used. C57BL/6J, a high-fat diet-induced obesity model mouse, was fed a high-fat diet containing BSCP or YSCP (20% fat) to induce obesity. The results showed that in the BSCP group, it caused significant suppression of body weight gain and suppression of white adipose tissue weight compared with the YSCP group. Moreover, it significantly decreased serum leptin levels, which correlated with visceral fat mass, and increased antidiabetic adipocytokine and adiponectin levels. Therefore, this suggests the pigmented components contained in BSCP have an antiobesity effect in obese model mice. It is suggested that this material, which can be prepared without extraction with an organic solvent and is suitable for use as a food material, could be a functional food material with a practicable antiobesity effect.
- Hirona Kugo; Wanida Sukketsiri; Hiroki Tanaka; Rena Fujishima; Tatsuya Moriyama; Nobuhiro ZaimaBiology 10 (2) 2021/02 [Refereed]
Hypoperfusion due to vasa vasorum stenosis can cause wall hypoxia and abdominal aortic aneurysm (AAA) development. Even though hypoperfusion is an important contributor toward pathological changes in AAA, the correlation between hypoperfusion and AAA is not fully understood. In this study, a time-dependent semi-quantitative pathological analysis of hypoperfusion-induced aortic wall changes was performed to understand the mechanisms underlying the gradual degradation of the aortic wall leading to AAA formation. AAA-related factors evaluated in this study were grouped according to the timing of dynamic change, and five groups were formed as follows: first group: angiotensin II type 1 receptor, endothelin-1 (ET-1), and malondialdehyde (MDA); second group: matrix metalloproteinase (MMP)-2, -9, -12, M1 macrophages (Mac387+ cells), and monocyte chemotactic protein-1; third group: synthetic smooth muscle cells (SMCs); fourth group: neutrophil elastase, contractile SMCs, and angiotensinogen; and the fifth group: M2 macrophages (CD163+ cells). Hypoxia-inducible factor-1α, ET-1, MDA, and MMP-9 were colocalized with alpha-smooth muscle actin cells in 3 h, suggesting that hypoperfusion-induced hypoxia directly affects the activities of contractile SMCs in the initial stage of AAA. Time-dependent pathological analysis clarified the cascade of AAA-related factors. These findings provide clues for understanding complicated multistage pathologies in AAA. - Yuki Takemoto; Chihiro Kishi; Yuki Sugiura; Yuri Yoshioka; Shinichi Matsumura; Tatsuya Moriyama; Nobuhiro ZaimaScientific reports 11 (1) 1728 - 1728 2021/01 [Refereed]
β-caryophyllene (BCP), an essential oil component of many herbs and spices, has various biological activities as a functional food factor. A distinct feature of BCP is its volatile double-ring sesquiterpene structure. Orally administered BCP is reportedly detected in its intact form in mice serum; however, the distribution of inhaled volatile BCP throughout the body remains unknown. This study aimed to estimate the distribution properties of inhaled volatile BCP and to investigate its effects on metabolism. After mice were exposed to volatile BCP, it was detected in the lung, olfactory bulb, brain, serum, heart, liver, kidney, epididymal fat, and brown adipose tissue. BCP was further detected in the brain, liver, and brown adipose tissue 24 h after exposure. Metabolites related to glutathione metabolism were significantly altered in the liver. These results suggest that inhaled volatile BCP is widely distributed in murine tissues and affects the dynamics of metabolites in the liver. - Eri Izumi; Shota Hidaka; Ayako Hiroi; Serina Kinugasa; Erika Yano; Nobuhiro Zaima; Tatsuya MoriyamaFoods (Basel, Switzerland) 10 (1) 2021/01 [Refereed]
Numerous recent studies have suggested that food allergens enter the skin and predispose individuals to food allergies through the production of IgE antibodies in the body. Cherries are a popular fruit eaten worldwide. However, cherries are an allergenic food and percutaneous sensitization with cherry allergens through the perioral region may occur while ingesting cherries. The identity of the cherry protein that triggers percutaneous sensitization in humans or animal models remains unknown. In this study, the backs of BALB/c mice were shaved and crude cherry extracts containing sodium dodecyl sulfate were applied to the skin. Thereafter, the cherry-specific IgE and IgG1 antibodies generated and secreted in response to the epidermal application were measured using an enzyme-linked immunosorbent assay or immunoblotting. Skin exposure to cherry extracts elevated cherry-specific IgG1 levels. Application of fractionated and purified cherry proteins (antigen candidates for percutaneous sensitization) that bound to the IgG1 antibodies led to the identification of a thaumatin-like protein (Pru av 2). This molecule is known as the major cherry allergen that affects humans. In conclusion, our study identified Pru av 2 as a cherry allergen that triggers percutaneous sensitization in mice for the first time. - Serina Kinugasa; Shota Hidaka; Serina Tanaka; Eri Izumi; Nobuhiro Zaima; Tatsuya MoriyamaFood & nutrition research 65 2021Background: Kiwifruit is a popular fruit consumed worldwide and is also used as a cosmetic ingredient. However, it is known to cause allergic reactions in humans. Recent studies have suggested an association between food allergy and food allergens entering the body via the skin. However, percutaneously sensitizing kiwifruit allergens have not been identified in human studies or in animal models. Objective: This study aimed to identify kiwifruit proteins that percutaneously sensitized mice through the epidermal application of crude extracts from green and gold kiwifruit on the dorsal skin, and serum IgE and IgG1 levels were used as sensitization markers. Design: BALB/c mice were back-shaved and their skin was exposed to crude extracts from green and gold kiwifruit that contained sodium dodecyl sulfate. Specific IgE and IgG1 antibodies generated and secreted in response to antigens were measured using enzyme-linked immunosorbent assay or immunoblotting. Results: Skin exposure to kiwifruit extract induced an increase in the levels of kiwifruit-specific IgE and IgG1, which are helper T cell 2-related allergenic antibodies in mice. These antibodies reacted with 18, 23, and 24 kDa proteins found in both green and gold kiwifruits. Thus, three percutaneously sensitizing allergens were identified and purified. Their amino acid sequences partially matched with that of kiwellin (Act d 5). Discussion and conclusion: Kiwellin has been identified as a plant defense-related protein. Interestingly, many plant allergens are biodefense-related proteins belonging to the pathogenesis-related protein family. Kiwellin, which was discovered to be a transdermal sensitizing antigen, might also be categorized as a biodefense-related protein. This study is the first to identify kiwellin (Act d 5) as a percutaneously sensitizing kiwifruit allergen in a mouse model.
- Hirotsugu Noguchi; Sohsuke Yamada; Ken-Ichi Hirano; Satoshi Yamaguchi; Akira Suzuki; Xin Guo; Nobuhiro Zaima; Ming Li; Kunihisa Kobayashi; Yoshihiko Ikeda; Toshiyuki Nakayama; Yasuyuki SasaguriHistology and histopathology 36 (1) 91 - 100 2021/01 [Refereed]
Genetic deficiency of adipose triglyceride lipase (ATGL), a rate-limiting enzyme for intracellular triglyceride (TG) hydrolysis, causes TG-deposit cardiomyovasculopathy (TGCV), a recently identified rare cardiovascular disorder (ORPHA code: 565612) in humans. One of the major characteristics of TGCV is a novel type of diffuse and concentric coronary atherosclerosis with ATGL-deficient smooth muscle cells (SMCs). Patients with TGCV have intractable coronary artery disease. Therefore, it is crucial to investigate the mechanisms underlying vascular lesions in ATGL deficiency using animal models. Cuff injury is an experimental procedure to induce vascular remodeling with neointimal formation with SMCs after placing a cuff around the adventitial side of the artery without direct influence on endothelium. We report the effect of cuff injury on femoral arteries of ATGL-knockout (ATGL⁻/⁻) mice. Cuff-induced concentric neointimal formation with migrating SMCs was exacerbated in ATGL⁻/⁻ mice, mimicking atherosclerotic lesions in patients with TGCV. In the media, cell death of SMCs and loss of elastic fibers increased. Perivascular infiltrating cells expressing tumor necrosis factor-α (TNF-α) were more prominent in ATGL⁻/⁻ mice than in wild-type (WT) mice. In Boyden chamber experiments, a greater number of ATGL⁻/⁻ SMCs migrated in response to TNF-α compared to WT SMCs. These data, for the first time, demonstrated that outside-in signaling by cuff-induced neointimal formation where paracrine stimuli from adventitial infiltrating cells may lead to neointimal formation and mediolysis in ATGL-deficient conditions. Cuff injury might be a valuable model for understanding the mechanisms underlying the development of atherosclerotic lesions in patients with TGCV. - Yuya Saga; Yudai Hatakenaka; Miho Matsumoto; Yuri Yoshioka; Shinichi Matsumura; Nobuhiro Zaima; Yoshiyuki KonishiNeuroreport 31 (18) 1302 - 1307 2020/12 [Refereed]
Ar-turmerone, which is a major bioactive component found in the essential oil derived from Curcuma longa, has been reported to inhibit proliferation and induce apoptosis in cancer cell lines. Recently, ar-turmerone has been reported to increase the proliferation of neuronal stem cells, in contrast to its actions in cancer cells. These observations raise the possibility that ar-turmerone serves specific functions in neuronal cell lineages. However, the effects of ar-turmerone on postmitotic neurons remain elusive. In the present study, we investigated the neuroprotective functions of ar-turmerone in primary cerebellar granule neuronal cultures. We found that ar-turmerone increased the survival of neurons following activity deprivation. Consistently, the induction of cleaved caspase-3, a hallmark of apoptosis, was prevented by ar-turmerone, although neither the level of reactive oxygen species nor the mitochondrial membrane potential was affected. This study reports a neuroprotective function for ar-turmerone, providing new insights into the potential therapeutic applications of ar-turmerone for neurological disorders. - Yoshimura Yukihiro; Nobuhiro ZaimaFoods (Basel, Switzerland) 9 (5) 2020/05 [Refereed]
Consuming food is essential for survival, maintaining health, and triggering positive emotions like pleasure. One of the factors that drive us toward such behavior is the presence of various compounds in foods. There are many methods to analyze these molecules in foods; however, it is difficult to analyze the spatial distribution of these compounds using conventional techniques, such as mass spectrometry combined with high-performance liquid chromatography or gas chromatography. Mass spectrometry imaging (MSI) is a two-dimensional ionization technology that enables detection of compounds in tissue sections without extraction, purification, separation, or labeling. There are many methods for ionization of analytes, including secondary ion mass spectrometry, matrix-assisted laser desorption/ionization, and desorption electrospray ionization. Such MSI technologies can provide spatial information on the location of a specific analyte in food. The number of studies utilizing MSI technologies in food science has been increasing in the past decade. This review provides an overview of some of the recent applications of MSI in food science and related fields. In the future, MSI will become one of the most promising technologies for visualizing the distribution of food components and for identifying food-related factors by their molecular weights to improve quality, quality assurance, food safety, nutritional analysis, and to locate administered food factors. - Ayato Matsuo; Kaho Matsushita; Ayano Fukuzumi; Naoki Tokumasu; Erika Yano; Nobuhiro Zaima; Tatsuya MoriyamaFoods (Basel, Switzerland) 9 (4) 2020/04 [Refereed]
Several analyses of allergen levels have been reported as part of the safety assessment of genetically modified (GM) soybean; however, few comprehensive analyses have included new allergens. Thus, in this study the levels of eight major soybean allergens, including Gly m 7 (a newly reported soybean allergen), were semi-quantitatively detected in six GM soybeans and six non-GM soybeans using antigen-immobilized ELISA and immunoblotting. We also analyzed the IgE-reactivity to these soybeans through immunoblotting, using sera from three soybean-allergic patients. The results showed that there were no significant differences in the levels of the major soybean allergens in the GM and non-GM soybeans. Moreover, there were no significant differences in the serum IgE-reactive protein profiles of the patients, as analyzed using immunoblotting. These results indicate that, in general, CP4-EPSPS-transfected GM soybeans are not more allergenic than non-GM soybeans. - Hirofumi Enomoto; Tomohiro Furukawa; Shiro Takeda; Hajime Hatta; Nobuhiro ZaimaFoods (Basel, Switzerland) 9 (2) 2020/02 [Refereed]
Phosphatidylcholine (PC) is the major phospholipid in meat and influences meat qualities, such as healthiness. PC is classified into three groups based on the bond at the sn-1 position: Diacyl, alkylacyl, and alkenylacyl. To investigate their composition and distribution in pork tissues, including longissimus thoracis et lumborum (loin) spinalis muscles, intermuscular fat, and transparent tissues, we performed matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI). Eleven diacyl-, seven alkylacyl-, and six alkenylacyl-PCs were identified using liquid chromatography (LC)-tandem MS (MS/MS) analysis. Despite many alkylacyl- and alkenylacyl-PC species sharing identical m/z values, we were able to visualize these PC species using MALDI-MSI. Diacyl- and alkylacyl- and/or alkenylacyl-PC species showed unique distribution patterns in the tissues, suggesting that their distribution patterns were dependent on their fatty acid compositions. PCs are a major dietary source of choline in meat, and the amount was significantly higher in the muscle tissues. Consumption of choline mitigates age-related memory decline and neurodegenerative diseases; therefore, the consumption of pork muscle tissues could help to mitigate these diseases. These results support the use of MALDI-MSI analysis for assessing the association between PC species and the quality parameters of meat. - Hiroki Tanaka; Nobuhiro Zaima; Hirona Kugo; Tatsuro Yata; Yasunori Iida; Keisuke Hashimoto; Chie Miyamoto; Takeshi Sasaki; Hideto Sano; Yuko Suzuki; Tatsuya Moriyama; Hideyuki Shimizu; Kazunori Inuzuka; Tetsumei Urano; Naoki UnnoAnnals of vascular surgery 63 382 - 390 0890-5096 2020/02 [Refereed]
Existing animal models do not replicate all aspects of abdominal aortic aneurysms (AAAs), including the rupture mechanisms. From histopathological analyses conducted in humans, it has been found that the vasa vasorum of the AAA wall is the starting point of circulatory failure and that bulging and dilatation of the abdominal aorta occurs through inflammation and tissue degeneration. We created a new animal model (the hypoperfusion-induced model) of AAAs. In this study, we describe the current animal models of AAAs and present the utility of our new model of AAAs. - Kiyoto Hoshino; Hirona Kugo; Chie Miyamoto; Keisuke Hashimoto; Hiroshi Murase; Masatoshi Mizuno; Tatsuya Moriyama; Nobuhiro ZaimaJournal of nutritional science and vitaminology 66 (1) 75 - 81 2020 [Refereed]
Abdominal aortic aneurysm (AAA) is a vascular disease characterized by weakening of vascular walls and progressive dilation of the abdominal aorta. Nicotine, the main component of tobacco, is reportedly associated with the development and rupture of AAA. It is desirable to attenuate the destructive effect of nicotine on vascular walls, using dietary food components. However, effective methods for preventing AAA progression using dietary food components remain unestablished. This study focuses on proanthocyanidins, well known for their potent antioxidant activity. We speculated that proanthocyanidins can suppress nicotine-induced weakening of vascular walls. To estimate the effect of black soybean seed coat extract (BSSCE), rich in proanthocyanidins, on nicotine-induced weakening of the aortic wall, mice were divided into four groups: the control diet and distilled water group (named C), BSSCE solution diet and distilled water group (named B), control diet and 0.5 mg/mL nicotine solution group (named CN), and BSSCE solution diet and 0.5 mg/mL nicotine solution group (named BN). Nicotine-induced degradation of elastin and collagen fibers were significantly suppressed in BN group. The positive areas for matrix metalloproteinase (MMP)-2 and oxidative stress in BN group were significantly decreased compared to those in CN group. These results suggest that proanthocyanidins-rich BSSCE can prevent the weakening of the aortic wall via inhibiting MMP-2 upregulation. - Tatsuya Moriyama; Erika Yano; Nobuhiro Zaima; Keiko Miyazaki; Kou Shirotsuki; Aki Sato; Makoto SawaguchiJournal of nutritional science and vitaminology 66 (3) 270 - 277 2020 [Refereed]
β-Conglycinin is the major storage protein in soybeans. Pre-clinical animal models and human clinical studies have demonstrated the triglyceride-lowering effect of this protein, suggesting that it could be put into practical use as a functional food material. To date, however, there are no accurate and simple assays for quantification of β-conglycinin. In this study, samples were pretreated by mixing them with rice flour powder prior to extraction of proteins. Then, we used commercially available ELISA kits for detection of allergens that could be present in any contaminating soybean residue. This enabled accurate and highly reproducible quantitation of β-conglycinin content in several processed soybean foods. - Michio Tanaka; Yoshihiko Ikeda; Ming Li; Nobuhiro Zaima; Yutaka Kawahara; Koji Watanabe; Tohru Inaba; Kunihisa Kobayashi; Hirotsugu Noguchi; Sohsuke Yamada; Hiroyuki Hao; Ken-Ichi HiranoPathology international 70 (1) 58 - 61 2020/01 [Refereed]
- Chie Miyamoto; Hirona Kugo; Keisuke Hashimoto; Tatsuya Moriyama; Nobuhiro ZaimaScientific reports 9 (1) 18330 - 18330 2019/12 [Refereed]
Abdominal aortic aneurysm (AAA) is a vascular disease characterized by weakening of the vascular walls. Male sex is a risk factor for AAA, and peak AAA incidence occurs in men 10 years earlier than in women. However, the growth rate of AAA is faster in women, and women have a higher mortality due to AAA rupture. The mechanisms underlying sex-related differences in AAA remain unknown. Herein, we evaluated the effects of ovariectomy (OVX) on AAA in rats. Upon evaluation of the effects of OVX and AAA induction, AAA incidence rate and the aneurysm diameter increased in the OVX group. However, the histopathology in the developed AAA wall was not different between groups. When the effects of OVX on the vascular wall without AAA induction were evaluated, elastin and collagen levels were significantly decreased. Furthermore, the level of matrix metalloproteinase-9 significantly increased in the OVX group. According to our results, it is speculated that decreased levels of collagen and elastin fibers induced by OVX might be involved in increased incidence rate and diameter of AAA. Weakening of the vascular wall before the onset of AAA might be one reason for the faster rate of AAA growth in women. - Wanida Sukketsiri; Kiyoto Hoshino; Hirona Kugo; Tomomi Nakamura; Tsukasa Sasoh; Tatsuya Moriyama; Nobuhiro ZaimaJournal of oleo science 68 (12) 1241 - 1249 1345-8957 2019/12 [Refereed]
Nicotine has been linked to the development of abdominal aortic aneurysms. Isoflavones, a group of polyphenolic compounds, reportedly exhibit antioxidant and anti-inflammatory properties and facilitate cardiovascular protection. However, the effects of isoflavone on nicotine-induced abdominal aortic aneurysms have not yet been elucidated. The objective of the current study was to evaluate the inhibitory effect of isoflavone on nicotine-induced weakening of the aortic wall in mouse models. Nicotine reportedly increases the occurrence of abdominal aortic aneurysms by activating endothelin-1 (ET-1), angiotensinogen and the angiotensin II type 1 (AT1) receptor, leading to an increase in neutrophil elastase, oxidative stress, and matrix metalloproteinase (MMP)-2 expression, which causes vascular wall weakness and damage. Immunohistological analyses have indicated that isoflavone significantly inhibits the activation of ET-1, angiotensinogen and the AT1 receptor in nicotine-administered mice. Additionally, isoflavone suppressed elastic fiber destruction and decreased areas positive for MMP-2, neutrophil elastase, and malondialdehyde in the vascular wall of nicotine-administered mice. Considered together, these findings suggest that isoflavone shows potential for preventing vascular wall injury induced by nicotine administration, and that food containing isoflavone may protect against abdominal aortic aneurysms. - Hirona Kugo; Tatsuya Moriyama; Nobuhiro ZaimaAdipocyte 8 (1) 229 - 239 2162-3945 2019/12 [Refereed]
Abdominal aortic aneurysm (AAA) is a vascular disease characterized by the dilation of the abdominal aorta, resulting in a high mortality rate caused by vascular rupture. Previous studies have suggested that the abnormal appearance of adipocytes in the vascular wall is associated with the development of AAA. However, the mechanisms underlying the appearance of the ectopic adipocytes remain unknown. In this study, we showed that CD44+CD90+ MSCs express adipogenic transcription factors in the AAA wall of a hypoperfusion-induced AAA model. The number of CD44+CD90+ cells and adipocytes in the AAA wall significantly decreased in the perivascular adipose tissue (PVAT)-removed vascular wall. The AAA diameter significantly decreased in the PVAT-removed vascular wall compared with that in the vascular wall with PVAT. These data suggested that PVAT plays important roles in the differentiation of MSCs into adipocytes in response to vascular hypoperfusion. The decreased number of adipocytes in the PVAT-removed vascular wall might be associated with the decreased AAA diameter. - Kazuko Iwamoto; Hirokazu Kawamoto; Fumiaki Takeshita; Shinichi Matsumura; Ikuto Ayaki; Tatsuya Moriyama; Nobuhiro ZaimaJournal of oleo science 68 (9) 923 - 930 1345-8957 2019/09 [Refereed]
Ginkgo biloba extract (GBE) is widely used as herbal medicine. Preventive effect of GBE against dementia, including Alzheimer's disease, has been reported. The bioactive compounds in GBE that impart these beneficial effects, flavonoids and terpene lactones, have poor bioavailability. Our previous study found distribution of bioactive compounds of sesame extract in mice brain after mixing it with turmeric oil. Here, we evaluate the distribution of bioactive compounds of GBE by combining it with the mixture of sesame extract and turmeric oil (MST). The content of terpene lactones in mice serum was significantly increased in a dose-dependent manner after administration of GBE. However, the contents of terpene lactones in mice brain were not significantly changed. Concentration of ginkgolide A in mice brain increased significantly when GBE was co-administrated with MST than when GBE was administered alone. These results suggest that MST may be effective in enhancing the bioavailability of ginkgolide A in GBE. - Hirofumi Enomoto; Shiro Takeda; Hajime Hatta; Nobuhiro ZaimaJournal of food science 84 (7) 1758 - 1763 0022-1147 2019/07 [Refereed]
Sphingomyelin (SM) species are major sphingolipids in pork meat that affect quality parameters, such as health benefits due to their protective properties against chronic diseases; however, their spatial distribution remains unclear. We used matrix-assisted laser desorption/ionization (MALDI)-imaging mass spectrometry (IMS) to investigate the distribution and composition of SM species in pork chop consisting of longissimus thoracis et lumborum muscle (loin), intermuscular fat tissue, transparent tissue, and spinalis muscle. Four SM species were identified by liquid chromatography-electrospray ionization-tandem MS (MS/MS) and MALDI-MS/MS and visualized using MALDI-IMS. SM species containing stearic acid were predominantly distributed in the loin and spinalis muscle, whereas SM species containing palmitic, lignoceric, and nervonic acids were predominantly distributed in transparent tissue. These results indicated that the distribution of SM species differed among the pork tissues, depending on the tissue-specific fatty acid composition. The total amount including all identified SM species was higher in the loin than in spinalis muscle. Pork is reportedly associated with increased risk for chronic diseases due to the high amount of heme iron. From the observation of color, the amount of heme iron was lower in loin than in spinalis muscle. Thus, the degree of risk for chronic diseases might be lower in the loin than in spinalis muscle. This is the first report on the tissue-specific distribution of SM species in meat at a microscopic resolution using IMS. MALDI-IMS analysis may be useful in assessing the association between SM species and quality parameters of pork meat. PRACTICAL APPLICATION: Sphingomyelin (SM) species are major sphingolipids in pork meat. SM species affect quality parameters such as health benefits due to their protective properties against colon cancer and atherosclerosis. Matrix-assisted laser desorption/ionization-imaging mass spectrometry analysis combined with liquid chromatography-electrospray ionization-tandem mass spectrometry is a suitable method to directly investigate the distribution and composition of SM species at microscopic level among different tissues of pork meat. Therefore, this method is useful to assess the SM species-induced health effect of different tissues of pork meat. - Ming Li; Ken-Ichi Hirano; Yoshihiko Ikeda; Masahiro Higashi; Chikako Hashimoto; Bo Zhang; Junji Kozawa; Koichiro Sugimura; Hideyuki Miyauchi; Akira Suzuki; Yasuhiro Hara; Atsuko Takagi; Yasuyuki Ikeda; Kazuhiro Kobayashi; Yoshiaki Futsukaichi; Nobuhiro Zaima; Satoshi Yamaguchi; Rojeet Shrestha; Hiroshi Nakamura; Katsuhiro Kawaguchi; Eiryu Sai; Shu-Ping Hui; Yusuke Nakano; Akinori Sawamura; Tohru Inaba; Yasuhiko Sakata; Yoko Yasui; Yasuyuki Nagasawa; Shintaro Kinugawa; Kazunori Shimada; Sohsuke Yamada; Hiroyuki Hao; Daisaku Nakatani; Tomomi Ide; Tetsuya Amano; Hiroaki Naito; Hironori Nagasaka; Kunihisa KobayashiOrphanet journal of rare diseases 14 (1) 134 - 134 2019/06 [Refereed]
Triglyceride deposit cardiomyovasculopathy (TGCV) is a phenotype primarily reported in patients carrying genetic mutations in PNPLA2 encoding adipose triglyceride lipase (ATGL) which releases long chain fatty acid (LCFA) as a major energy source by the intracellular TG hydrolysis. These patients suffered from intractable heart failure requiring cardiac transplantation. Moreover, we identified TGCV patients without PNPLA2 mutations based on pathological and clinical studies. We provided the diagnostic criteria, in which TGCV with and without PNPLA2 mutations were designated as primary TGCV (P-TGCV) and idiopathic TGCV (I-TGCV), respectively. We hereby report clinical profiles of TGCV patients. Between 2014 and 2018, 7 P-TGCV and 18 I-TGCV Japanese patients have been registered in the International Registry. Patients with I-TGCV, of which etiologies and causes are not known yet, suffered from adult-onset severe heart disease, including heart failure and coronary artery disease, associated with a marked reduction in ATGL activity and myocardial washout rate of LCFA tracer, as similar to those with P-TGCV. The present first registry-based study showed that TGCV is an intractable, at least at the moment, and heterogeneous cardiovascular disorder. - Kazuko Iwamoto; Shinichi Matsumura; Yuri Yoshioka; Ayami Yamamoto; Shohei Makino; Tatsuya Moriyama; Nobuhiro ZaimaLipids 54 (5) 311 - 320 0024-4201 2019/05 [Refereed]
Accumulation of amyloid-β peptide is associated with Alzheimer's dementia. Previously, we reported that sesamin and sesamolin inhibited β-secretase activity in vitro, and each was transported to the serum and brain in mice after oral administration. However, the bioavailability of sesamin and sesamolin was poor in mice. In this study, we aimed to improve the bioavailability of sesamin and sesamolin. We found that the levels of sesamin and sesamolin in mouse serum and brain were higher after the administration of a mixture of sesame extract and turmeric oil (MST) than those after administering sesame extract alone. Serum sesamin and sesamolin contents in the MST-treated group were 23-fold and 15-fold higher, respectively, than those in the sesame extract-treated group. Brain sesamin and sesamolin contents in the MST-treated group were 14-fold and 11-fold higher, respectively, than those in the sesame extract-treated group. These results suggest that turmeric oil is an effective solvent to enhance the bioavailability of sesamin and sesamolin. - Hirona Kugo; Chie Miyamoto; Ayaka Sawaragi; Kiyoto Hoshino; Yuka Hamatani; Shinichi Matsumura; Yuri Yoshioka; Tatsuya Moriyama; Nobuhiro ZaimaJournal of oleo science 68 (1) 79 - 85 1345-8957 2019 [Refereed]
Abdominal aortic aneurysm (AAA) is a vascular disease characterized by the weakening of the vascular walls and the progressive dilation of the abdominal aorta. Nicotine, a primary component of cigarette smoke, is associated with AAA development and rupture. Nicotine induces AAA development by weakening vascular walls. However, little is known about preventive methods using functional food factors for nicotine-induced vascular destruction. Sesamin and sesamolin are functional food factors that are fat-soluble lignans found in Sesamum indicum seeds. Previous reports indicated that sesamin and sesamolin have anti-oxidative and anti-inflammatory effects. In this study, we evaluated the effects of sesamin and sesamolin-rich sesame extract on the weakening of vascular walls in nicotine-administered mice. Sesame extract attenuated the degradation of collagen and elastin fibers caused by nicotine. In addition, sesame extract decreased the area positive for matrix metalloproteinase 12 (MMP-12) and oxidative stress in the vascular walls. These results suggest that sesame extract may decrease the weakening of vascular walls by suppressing the nicotine-induced degradation of collagen and elastin fibers. Sesame extract may be effective in preventing AAA development by decreasing both, MMP-12 expression and oxidative stress in vascular walls. - Kazuko Iwamoto; Shuichi Kamo; Yuichi Takada; Ayana Ieda; Takatoshi Yamashita; Toshiro Sato; Nobuhiro Zaima; Tatsuya MoriyamaBiochemistry and biophysics reports 16 44 - 49 2018/12 [Refereed]
Soyasapogenol is a soyasaponin aglycone, which has been suggested to exert a more potent function than the glycoside form. In this study, the effect of soyasapogenol A and B on cultured adipocyte cell function was investigated using mouse 3T3-L1 adipocyte cells. 3T3-L1 cells were treated with insulin, dexamethasone, and 3-isobutyl-1-methylxanthine for differentiation to adipocytes, and the cells were then cultured in the presence of soyasapogenol A or B (6.25 or 12.5 µM). The media were harvested and refreshed every 2 d. After a 10 d culture, the cells were harvested and the triglyceride content of the cells was determined. The triglyceride content of soyasapogenol B-treated cells was significantly lower than those of vehicle-treated cells. Glycerol and free fatty acid levels in the soyasapogenol-treated cell media were higher than those in vehicle cells. However, there was no difference in the level of adipose triglyceride lipase among soyasapogenol A-, soyasapogenol B-, and vehicle-treated cells. The secreted adiponectin and resistin levels of soyasapogenol-treated cell media were also different compared with those of vehicle-treated cells. Especially, the secreted resistin level in soyasapogenol B-treated cell media was obviously reduced compared with that of vehicle-treated cells. Taken together, these results suggest that soyasapogenol B exerted an anti-obesity and anti-diabetic effect on adipocytes by lowering the cellular triglyceride level by accelerating triglyceride lipolysis with reduced resistin secretion. - Hiroki Murakami; Takashi Ogawa; Akiho Takafuta; Erika Yano; Nobuhiro Zaima; Tatsuya MoriyamaBioscience, biotechnology, and biochemistry 82 (8) 1408 - 1416 0916-8451 2018/08 [Refereed]
Cutaneous exposure to food allergens can predispose individuals to food allergies. Soybean, a major allergenic food, is an ingredient in various cosmetic products. However, the types of soybean proteins that are percutaneously sensitizing in humans or animal models remain unknown. In this study, BALB/c mice were dorsally shaved and epicutaneously exposed to a crude soybean extract including sodium dodecyl sulfate or distilled water alone. Specific IgEs secreted in response to 7S globulin (Gly m 5), 11S globulin (Gly m 6), Gly m 3, and Gly m 4 were measured using enzyme-linked immunosorbent assays or immunoblots. Exposure to soybean extract elicited the secretion of soybean-specific IgEs. Of the soybean proteins, 7S and 11S globulins acted as percutaneous sensitizers in 6/9 mice (67%). Additionally, IgE bound specifically and preferentially to the 7S globulin β subunit. In conclusion, this is the first report to identify percutaneously sensitizing soybean allergens in a mouse model. - Kayo Hanafusa; Hiroki Murakami; Takuya Ueda; Erika Yano; Nobuhiro Zaima; Tatsuya MoriyamaBioscience, biotechnology, and biochemistry 82 (7) 1207 - 1215 0916-8451 2018/07 [Refereed]
The levels of food allergens in worm-wounded or non-wounded green soybeans (edamame) and mature soybeans were investigated by immunoblotting and enzyme-linked immunosorbent assay (ELISA), using allergen-specific antibodies. Non-wounded and worm-wounded soybeans showed similar total protein profiles after Coomassie brilliant blue staining, but some protein bands were observed to have been changed by worm wounding. Immunoblotting with specific antibodies for major soybean allergens (Gly m 5, Gly m 6, Gly m Bd 30 K, and Kunitz soybean trypsin inhibitor) revealed that protein band profiles and intensities were not significantly changed by worm wounding. In contrast, levels of the pollen-related soybean allergens Gly m 4 and Gly m 3 were strongly increased by worm wounding in both green and mature soybeans, as detected by immunoblotting and ELISA. These results suggested that the pollen-related food allergen risk (i.e., oral allergy syndrome; OAS) from soybeans might be enhanced by worm wounding of soybeans. - Hirona Kugo; Hiroki Tanaka; Tatsuya Moriyama; Nobuhiro ZaimaAnnals of vascular diseases 11 (2) 159 - 168 1881-641X 2018/06 [Refereed]
Abdominal aortic aneurysm (AAA) is a vascular disease that involves the gradual dilation of the abdominal aorta followed by its rupture. AAA is closely associated with weakening of the vascular wall due to oxidative stress, chronic inflammation, and degradation of the extracellular matrix. No effective drug therapy is currently available for preventing aneurysm progression or rupture. Adipocytes in the vascular wall are reportedly closely associated with AAA development and rupture. Fiber degradation in the aneurysm wall is enhanced by increased numbers of adipocytes, and rupture risk may increase as well. Recent studies suggested that appropriate control of adipocytes in the vascular wall may be an important strategy to prevent AAA rupture, and further studies may aid in the establishment of a method for preventing AAA rupture by therapeutic drugs or functional foods. In this review, we summarize adipocyte function and the correlation between AAA and adipocytes. - Chie Miyamoto; Hirona Kugo; Keisuke Hashimoto; Ayaka Sawaragi; Nobuhiro Zaima; Tatsuya MoriyamaJournal of oleo science 67 (5) 589 - 597 1345-8957 2018/05 [Refereed]
Abdominal aortic aneurysm (AAA) is a vascular disease that results in rupture of the abdominal aorta. The risk factors for the development of AAA include smoking, male sex, hypertension, and age. AAA has a high mortality rate, but therapy for AAA is restricted to surgery in cases of large aneurysms. Clarifying the effect of dietary food on the development of AAA would be helpful for patients with AAAs. However, the relationship between dietary habits and the development of AAA is largely unknown. In our previous study, we demonstrated that adipocytes in vascular wall can induce the rupture of AAA. Therefore, we focused on the diet-induced abnormal triglyceride metabolism, which has the potential to drive AAA development. In this study, we have evaluated the effects of a high-sucrose diet on the development of AAA in a vascular hypoperfusion-induced animal model. A high sucrose diet induced high serum TG level and fatty liver. However, the AAA rupture risk and the AAA diameter were not significantly different between the control and high-sucrose groups. The intergroup differences in the elastin degradation score and collagen-positive area were insignificant. Moreover, matrix metalloproteinases, macrophages, and monocyte chemoattractant protein-1-positive areas did not differ significantly between groups. These results suggest that a high-sucrose diet does not affect the appearance of vascular adipocyte and AAA development under the vascular hypoperfusion condition. - Hiroki Tanaka; Yasunori Iida; Takayuki Iwaki; Yuko Suzuki; Hideto Sano; Chiharu Miyajima; Nobuhiro Zaima; Takeshi Sasaki; Ayato Sumioka; Shogo Hakamata; Hideyuki Shimizu; Kazuo Umemura; Tetsumei UranoAnnals of vascular surgery 48 204 - 213 0890-5096 2018/04 [Refereed]
BACKGROUND: Plasma low-density lipoprotein (LDL) cholesterol is implicated in abdominal aorta (AA) and aortic dissection (AD); however, its role in the pathogenesis of AA and AD, a disease with a high mortality rate, is unknown. The existing animal models such as apolipoprotein E-deficient (Apoe-/-) mice cannot reproduce all the conditions of AA/AD, including elevated LDL-cholesterol levels and spontaneous atheroma formation; therefore, a more reliable in vivo model is required. Here, we analyzed angiotensin II (Ang II)-induced mice with combined deficiency of the LDL receptor and the catalytic component of the apolipoprotein B-edisome complex (Ldlr-/-/Apobec1-/- [WKO]) to understand AA formation and AD occurrence in relation to plasma lipid composition. METHODS: AAs and ADs were created in 18- to 22- week-old male Apoe-/- and Ldlr-/-/Apobec1-/- mice by Ang II infusion. Immunostaining allowed assessment of smooth muscle cells and mural monocytes/macrophages. RESULTS: Ldlr-/-/Apobec1-/- mice had elevated LDL-cholesterol levels characteristic for human type IIa hyperlipidemia, resulting in atherogenesis, which promoted mortality, AA formation, and AD development. Interestingly, variations in the distribution of atheromas and inflammatory sites between Apoe-/- and Ldlr-/-/Apobec1-/- mice depending on lipid profiles resulted in differences in AA formation and AD occurrence in the thoracic aorta. CONCLUSIONS: Our results indicate the presence of a pathogenic pathway involving serum lipid composition that plays a key role in AA formation and AD occurrence in Ang II-induced mice. - Shuhei Yamada; Nobuhiro Zaima; Yukihiro Yoshimura; Shiori Inaba; Takamichi Fujimori; Tetsuya Sogon; Tatsuya MoriyamaRapid Communications in Mass Spectrometry John Wiley and Sons Ltd 32 (5) 380 - 384 1097-0231 2018/03 [Refereed]
Rationale: Anthocyanins, which belong to a class of molecules called flavonoids, are known to have beneficial effects for both humans and animals. Many physiological functions have been attributed to anthocyanins since ancient times. The most important function is the relief of eyestrain, but the biodistribution of anthocyanins remains unknown. In this study, we analyzed the kinetics of anthocyanin species in mice eyeballs and surrounding tissues. Methods: We used mice that were administered bilberry extract solution intraperitoneally. After harvesting eyeballs, cross-sections were prepared using a cryostat and analyzed using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). Results: Various ions of anthocyanin species, m/z 419, 449, 463, 465, 479, and 493, were observed in MALDI-MSI spectra. Most of these peaks corresponded to places considered to be extraocular muscles with the outer layer of the retina. Conclusions: Through MALDI-MSI and MALDI-MS/MS analyses, we demonstrated that anthocyanin species are distributed at muscle tissues with the outer layer of the retina. It is speculated that anthocyanin species directly improve eyestrain at the extraocular muscles. - Shuichi Kamo; Yuichi Takada; Takatoshi Yamashita; Toshiro Sato; Erika Yano; Nobuhiro Zaima; Tatsuya MoriyamaJournal of nutritional science and vitaminology 64 (3) 222 - 228 0301-4800 2018 [Refereed]
Group B soyasaponins, found in soy, have various health-promoting properties, but it is unclear whether they have an anti-obesity effect. The aim of this study was to evaluate the anti-obesity effect of group B soyasaponin glycosides and aglycone in mice fed a high-fat diet. Six-week-old C57/BL6 mice were divided into three groups (each n=10) and orally administered a high-fat diet for 35 d; two of the groups also received group B soyasaponin glycosides or aglycone. Although there was no significant difference among the three groups in consumption, the weight of fat adipose tissue at autopsy was more than 30% lower in the group B soyasaponin aglycone group than in the control group, but X-ray computed tomography showed no significant difference in muscle weight between these two groups. The ratio of muscle to whole body weight was higher in the group B soyasaponin aglycone group than in the control group. These results suggest that group B soyasaponin aglycone has a stronger anti-obesity effect than group B soyasaponin glycosides, without a loss in muscle weight, and that it increases the ratio of muscle to whole body weight. To our knowledge, this is the first report showing the anti-obesity effect of soyasaponin aglycone in vivo using animal models. - Kugo H; Moriyama T; Zaima NCurrent drug targets 19 (11) 1228 - 1232 1389-4501 2018/01 [Refereed]
- Keisuke Hashimoto; Hirona Kugo; Hiroki Tanaka; Kazuko Iwamoto; Chie Miyamoto; Tetsumei Urano; Naoki Unno; Kohsuke Hayamizu; Nobuhiro Zaima; Tatsuya MoriyamaJournal of vascular research 55 (2) 63 - 74 1018-1172 2018 [Refereed]
Abdominal aortic aneurysm (AAA) is a vascular disease characterized by chronic inflammation in the infrarenal aorta. Most cases of AAA remain asymptomatic until rupture, and the mortality rate of patients with AAA rupture is very high. Currently, the relation between dietary habits and AAA development remains unknown. In this study, we evaluated the effects of a high-fat diet on the development of AAA in a vascular hypoperfusion-induced animal model. The risk of AAA rupture and AAA diameter in the high-fat group significantly increased compared with those in the control group. The number and size of adipocytes in the vascular wall in the high-fat group significantly increased as compared with those in the control group. Additionally, the collagen-positive sections in the areas with adipocytes significantly decreased as compared with those without adipocytes. The protein levels of matrix metalloproteinase (MMP)-2, MMP-9, and MMP-12, and macrophage-positive areas in the parts with adipocytes also significantly increased as compared with those without adipocytes. These data suggested that AAA rupture risk increased through accelerating chronic inflammation due to the accumulation of adipocytes in the vascular wall in the high-fat group. - Hirona Kugo; Yoshihiko Ikeda; Tatsuya Moriyama; Nobuhiro ZaimaJournal of oleo science 67 (12) 1543 - 1549 1345-8957 2018 [Refereed]
Thoracic aortic aneurysm (TAA) is a lethal vascular disease that involves localized dilation of the thoracic aorta. The detailed mechanisms of TAA development and rupture are not fully understood. Recent reports have shown that the abnormal appearance of adipocytes in the vascular wall is associated with abdominal aortic aneurysm (AAA) progression or rupture. However, the presence of adipocytes in the TAA wall remains unknown. In this study, we observed the pathology of thoracic aortae to investigate whether adipocytes abnormally appear in the TAA wall. Abnormal appearance of adipocytes was mainly observed in the adventitia in the TAA vascular walls. The adipocyte area in the vascular wall was significantly increased in the TAA wall compared to the control wall. Destruction of collagen fibers, and increase in areas positive for matrix metalloproteinase (MMP) -2, MMP-9, and Mac387+ macrophages were observed in the area around adipocytes in the vascular wall. This study demonstrated the appearance of adipocytes in the TAA wall. The accumulation of adipocytes in AAA wall reportedly facilitates the destruction of fibers surrounding adipocytes, and thereby, leads to vascular wall weakness. Therefore, adipocytes in the TAA wall can be associated with the weakening of the vascular wall as well as the AAA wall. The appropriate control of adipocytes in the vascular wall may prevent weakening of the vascular wall in TAA. - Hiroki Murakami; Takashi Ogawa; Akiho Takafuta; Erika Yano; Nobuhiro Zaima; Tatsuya MoriyamaJournal of nutritional science and vitaminology 64 (6) 483 - 486 0301-4800 2018 [Refereed]
Oral tolerance prevents allergic responses, but cutaneous exposure to food allergens predisposes individuals to food allergies. Soybean, a major allergenic food, is also an ingredient in various cosmetic products. However, it remains to be determined whether oral tolerance prevents percutaneous sensitization to soybean proteins in humans or animal models. In this study, BALB/c mice were divided into three groups; the SS group fed a soybean-containing diet, and the CS and control (C) groups fed a soybean-free diet. After being dorsally shaved, the CS and SS groups were epicutaneously exposed to a soybean extract while the control group was exposed to only the carrier. Specific IgE and IgG1 immunoglobulins secreted in response to the soybean proteins were measured using enzyme-linked immunosorbent assays. Exposure to the soybean extract elicited the secretion of IgE and IgG1 specific for Gly m 5 and Gly m 6, and trypsin inhibitor. Oral soybean consumption attenuated the secretion of all the soybean-specific IgEs and IgG1s, suggesting that percutaneous sensitization to soybean proteins is attenuated by oral tolerance. - Keisuke Hashimoto; Nobuhiro Zaima; Hirotaka Sekiguchi; Hirona Kugo; Chie Miyamoto; Kiyoto Hoshino; Natsumi Kawasaki; Keita Sutoh; Koji Usumi; Tatsuya MoriyamaJournal of nutritional science and vitaminology 64 (4) 271 - 276 0301-4800 2018 [Refereed]
Abdominal aortic aneurysm (AAA) is a vascular disease characterized by chronic inflammation in the infrarenal aorta. Epidemiologic data have clearly linked tobacco smoking to aneurysm formation and a faster rate of expansion. It suggested that nicotine, one of the main ingredients of tobacco, has been suggested to be associated with AAA development and rupture. In the condition where no established drugs are available; therefore, an effective approach to prevent the vascular damage from nicotine consumption may be the use of dietary functional food factors. However, little is known about the relationship between dietary components and AAA. In this study, we estimated the effect of dietary deoxyribonucleic acid (DNA) on the vascular wall. After habituation for 5 d, the mice were divided into four groups: control diet and distilled water group (C), DNA-Na diet and distilled water group (DNA), control diet and 0.5 mg/mL nicotine solution group (C-Nic), DNA-Na diet, and 0.5 mg/mL nicotine solution group (DNA-Nic). The dietary DNA attenuated the degradation of elastin fibers induced by nicotine administration. The areas stained positive for MMP-2 in the DNA-Nic group were significantly suppressed compared to C-Nic mice. These data suggest that the dietary DNA may prevent the weakening of the aortic wall via inhibition of the MMP-2-dependent pathway. In conclusion, we have revealed the protective effect of dietary DNA on the vascular pathology of nicotine-administrated mice. A nucleic acid-rich diet might be useful for people who consume nicotine via smoking, chewing tobacco, or nicotine patches. - Hiroki Tanaka; Naoki Unno; Tatsuro Yata; Hirona Kugo; Nobuhiro Zaima; Takeshi Sasaki; Tetsumei UranoJOVE-JOURNAL OF VISUALIZED EXPERIMENTS JOURNAL OF VISUALIZED EXPERIMENTS (129) 1940-087X 2017/11 [Refereed]
The adventitial vasa vasorum (VV) provides oxygen and nourishment to the aortic wall. Hypoxia in the aortic wall can cause enlarged abdominal aortic aneurysms (AAAs). This article introduces and describes a standard protocol used to induce AAAs through adventitial VV hypoperfusion created with a combination of polyurethane catheter insertion into the aortic lumen and suture ligation of the infrarenal abdominal aorta. The protocol involves the use of male rats weighing 300-400 g, which are provided food and water ad libitum. After laparotomy with a ventral midline abdominal incision, exfoliation of the aorta is performed, which blocks blood flow from the perivascular tissue. Aortotomy involving a small incision adjacent to the renal artery branches is performed, and a polyurethane catheter is inserted using an 18-gauge indwelling needle. After repairing the incision, tight ligation of the aorta over the catheter blocks VV blood flow from the proximal direction through the aortic wall without disturbing the aortic blood flow. This technique can induce an AAA with progressive aortic dilatation. The greatest benefit of this model is that VV hypoperfusion causes tissue hypoxia and the development of an infrarenal AAA, which has morphological and pathological characteristics similar to those of a human AAA. - Teruyoshi Tanaka; Nobuhisa Kawaguchi; Nobuhiro Zaima; Tatsuya Moriyama; Yasuhisa Fukuta; Norifumi ShirasakaJOURNAL OF NATURAL MEDICINES SPRINGER JAPAN KK 71 (4) 632 - 641 1340-3443 2017/10 [Refereed]
In recent years, the number of patients with osteoporosis has risen with the increase in average longevity. Therefore, the chemoprevention of osteoporosis using food materials or food components has become an increasingly important target. Syringic acid (SA) is a phenolic compound present in the fruit of the a double dagger ai palm Euterpe oleracea and the mycelium of the shiitake mushroom Lentinula edodes. This compound has no affinity for estrogen receptors and is potentially useful for disease prevention. However, little is known about the effects of a SA diet on bone metabolism, particularly bone resorption in vivo. Here, we demonstrated the effects of a SA diet on bone loss and uterine weight loss in ovariectomized (OVX) mice. Ten-week-old OVX mice were fed SA-containing diets (100 mg/kg body weight/day) for 10 weeks. After 10 weeks of dietary SA, the body weight, food intake, and uterine weight of the OVX mice were unaffected; however, femoral bone mineral density (cortical bone density, cancellous bone density, and total bone density) was higher in the SA-fed groups than in the OVX-control group. Furthermore, histomorphometric analysis revealed that the number of osteoclasts and osteoblasts was decreased and increased, respectively, in the SA-fed groups. These results suggest that a SA diet suppresses bone loss by downregulating bone resorption and upregulating bone formation without affecting the uterus in OVX mice. Although further studies are needed, SA may be a compound that can be used to prevent or retard osteoporosis. - Higashi M; Ikeda Y; Miyauchi H; Zaima N; Suzuki A; Li M; Kobayashi K; Naito H; Hirano KAnnals of Nuclear Cardiology Japanese Society of Nuclear Cardiology 3 (1) 94 - 102 2017/08 [Refereed]
Triglyceride deposit cardiomyovasculopathy (TGCV) is a novel clinical entity we found in patients with severe heart failure waiting for cardiac transplantation. The probands carried genetic mutations in adipose triglyceride lipase (ATGL), which is an essential molecule for the intracellular hydrolysis of TG. Patients with TGCV showed ectopic accumulation of TG in cardiomyocytes and smooth muscle cells resulting from the abnormal intracellular metabolism of TG and its substrates, long chain fatty acids (LCFAs). Our postmortem analyses demonstrated substantial numbers of autopsied individuals with TGCV phenotype, whose expression of ATGL was conserved. These results suggest that TGCV might be difficult to diagnose in daily clinics, however be more prevalent than expected, and a possible important cause of cardiac death. This review article focuses on imaging modalities to evaluate cardiomyovascular TG accumulation of this novel disease. Data and images are shown from pathological analyses, imaging mass spectrometry, myocardial scintigraphy with a radioactive analogue for LCFA, iodine-123-β-methyl iodophenyl-pentadecanoic acid, MR spectroscopy, and CT-based TG imagings in primary TGCV patients with genetic ATGL deficiency, which is ultra-rare, but the monogenic model. - Hirona Kugo; Nobuhiro Zaima; Megumi Onozato; Chie Miyamoto; Keisuke Hashimoto; Kenichi Yanagimoto; Tatsuya MoriyamaFOOD & FUNCTION ROYAL SOC CHEMISTRY 8 (8) 2829 - 2835 2042-6496 2017/08 [Refereed]
Abdominal aortic aneurysm (AAA) is a vascular disease involving gradual dilation of the abdominal aorta. Recent studies suggest that nicotine, which is a primary component in cigarette smoke, is closely associated with the development and rupture of an AAA. Nicotine accelerates AAA development through the weakening of the vascular wall by increasing oxidative stress and matrix metalloproteinase (MMP)-2 expression. However, little is known about preventing the AAA induced by nicotine. A non-surgical means of preventing the weakening of the vascular wall before the onset of AAA by functional food factors would be a valuable option over surgery. Fish oil is a functional food that is rich in n-3 polyunsaturated fatty acids that have an anti-inflammatory effect. In this study, we evaluated the effect of dietary fish oil on the weakening of the aortic wall due to nicotine administration in a mouse model. Histological analysis showed that the dietary fish oil suppressed the degradation of elastin fibers in the nicotine-administered mice. Additionally, the dietary fish oil suppressed the protein level of MMP-12, macrophage infiltration, and the oxidative stress in the vascular wall. These results suggest that fish oil could suppress the weakening of the vascular wall by suppressing the elastin fiber degradation caused by nicotine. By suppressing the nicotine induced weakening of the vascular wall, fish oil might help prevent the development of AAA. - Hirona Kugo; Nobuhiro Zaima; Hiroki Tanaka; Keisuke Hashimoto; Chie Miyamoto; Ayaka Sawaragi; Tetsumei Urano; Naoki Unno; Tatsuya MoriyamaJOURNAL OF OLEO SCIENCE JAPAN OIL CHEMISTS SOC 66 (5) 499 - 506 1345-8957 2017/05 [Refereed]
Abdominal aortic aneurysm (AAA) is a vascular disease that results in the gradual dilation of the abdominal aorta and has a high rupture-related mortality rate. However, the mechanism of AAA rupture remains unknown. In our previous study, we established a novel AAA animal model (hypoperfusion-induced AAA rat model) with spontaneous AAA rupture. Using the hypoperfusion-induced AAA rat model, we demonstrated that the abnormal appearance of adipocytes in the vascular wall is associated with AAA rupture. However, pathological analysis of the rupture area has not been performed because it is particularly difficult to identify the rupture point. In this study, we succeeded in obtaining samples from the rupture point and performed a histological analysis of the ruptured area in the vascular wall in the hypoperfusion-induced AAA rat model. Adipocytes were observed along the AAA-ruptured area of the vascular wall. In the areas around the adipocytes, macrophage infiltration and protein levels of matrix metalloproteinases 2 and 9 were significantly increased and collagen-positive areas were significantly decreased, as compared with areas without adipocytes. The AAA diameter was correlated with the number of adipocytes in the vascular wall of the hypoperfusion-induced AAA rat model. On the other hand, serum triglyceride levels and serum total cholesterol levels were not correlated with the number of adipocytes in the vascular wall. These results suggest that local adipocyte accumulation in the vascular wall, not serum lipids, has an important role in AAA rupture. - Teruyoshi Tanaka; Yuichiro Takei; Nobuhiro Zaima; Tatsuya Moriyama; Dai YamanouchiJOURNAL OF NUTRITIONAL SCIENCE AND VITAMINOLOGY CENTER ACADEMIC PUBL JAPAN 63 (1) 28 - 34 0301-4800 2017/02 [Refereed]
There have been reports that hyperglycemia suppresses osteoclast (OCL) differentiation, although the underlying mechanism is poorly understood. Here we demonstrated that high glucose suppresses OCL differentiation through activation of liver X receptor (LXR) beta, a recently reported glucose-sensing nuclear receptor. The effect of hyperglycemia on osteoclastogenesis was tested in RAW264.7 cells, a murine macrophage cell line. Cells were treated with receptor activator of NF-kappa B ligand (RANKL) under normoglycemic (5.5 mM glucose), normoglycemic with high osmotic pressure (5.5 mM glucose + 10.0 mM mannitol), and hyperglycemic (15.5 mM glucose) conditions. RANKL-induced osteoclastogenesis was significantly suppressed by high-glucose treatment. Mannitol treatment also significantly suppressed osteoclastogenesis, but the inhibitory effect was lower than for high-glucose treatment. The suppression of mRNA expression of Lxr beta by RANKL was significantly restored by high glucose, but not mannitol. Additionally, the deactivation of Lxr beta by siRNA attenuated high-glucose-induced suppression of osteoclastogenesis. Although further validation of the underlying pathway is necessary, targeting LXR beta is a potential therapeutic approach to treating osteoporosis. - Tanaka Hiroki; Zaima Nobuhiro; Sasaki Takeshi; Konno Hiroyuki; Setou Mitsutoshi; Unno NaokiANNALS OF VASCULAR DISEASES 10 (1) 78 1881-641X 2017 [Refereed]
- H. Kugo; N. Zaima; H. Tanaka; T. Urano; N. Unno; T. MoriyamaBIOTECHNIC & HISTOCHEMISTRY TAYLOR & FRANCIS INC 92 (2) 141 - 148 1052-0295 2017 [Refereed]
Abdominal aortic aneurysm (AAA) is the progressive dilation of the abdominal aorta. Nicotine is reported to be associated with the development and rupture of AAA, but the pathological effects of nicotine on normal rat aorta have not been determined. We investigated pathological changes in the aortic wall of rats caused by the administration of nicotine. Nicotine administration weakened the vascular wall, increased gelatinolytic activity and promoted the destruction of elastin and collagen in the rat abdominal aorta. There were no differences in the areas positive for matrix metalloproteinase (MMP)-2 and MMP-9 between the control and nicotine treated groups. The areas positive for MMP-12 in the nicotine group were significantly greater than for the control group. Gelatinolytic activity in the aortic wall was increased significantly in the nicotine group. Our findings suggest that MMP-12 is sensitive to nicotine exposure in rats. - Nobuhiro ZaimaJournal of Atherosclerosis and Thrombosis Japan Atherosclerosis Society 24 (9) 908 - 909 1880-3873 2017 [Refereed]
- Hiroki Tanaka; Nobuhiro Zaima; Takeshi Sasaki; Naoto Yamamoto; Kazunori Inuzuka; Tatsuro Yata; Takayuki Iwaki; Kazuo Umemura; Hideto Sano; Yuko Suzuki; Tetsumei Urano; Mitsutoshi Setou; Naoki UnnoJOURNAL OF VASCULAR RESEARCH KARGER 54 (4) 200 - 208 1018-1172 2017 [Refereed]
Free arachidonic acid (AA) is an important precursor of lipid mediators such as leukotrienes and prostaglandins that induces inflammation and is associated with atherosclerosis progression. Recent studies have shown that lysophosphatidylcholine acyltransferase-3 (LPCAT3) converts lysophosphatidylcholine (LPC) and free AA into phosphatidylcholine (PC)-containing AA (arachidonyl-PC) and thereby can regulate intracellular free-AA levels. However, the association between LPCAT3 and atherosclerosis remains to be established. In this study, we analyzed human and mouse atherosclerotic tissues to gain insight into the arachidonyl-PC metabolism involving LPCAT3 using imaging mass spectrometry. The data revealed a complementary distribution of arachidonyl-PC and LPC in human atherosclerotic tissues with arachidonyl-PC decreasing and LPC increasing as atherosclerosis progressed. Furthermore, we found a homologous distribution of LPCAT3 expression and arachidonyl-PC based on atherosclerotic progression. In contrast, in ApoE-deficient mice, atherosclerosis increased both arachidonyl-PC accumulation and LPCAT3 expression. Taken together, these findings suggest that the regulation of LPCAT3 expression might be associated with atherosclerotic progression in humans. (C) 2017 S. Karger AG, Basel - Yukihiro Yoshimura; Naoko Goto-Inoue; Tatsuya Moriyama; Nobuhiro ZaimaFOOD CHEMISTRY ELSEVIER SCI LTD 210 200 - 211 0308-8146 2016/11 [Refereed]
Food contains various compounds that have an impact on our daily lives. Many technologies have been established to analyze these molecules of interest in foods. However, the analysis of the spatial distribution of these compounds in foods using conventional technology, such as high-performance liquid chromatography-mass spectrometry or gas chromatography-mass spectrometry is difficult. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is considered an ideal complementary approach. MALDI-MSI is a two-dimensional MALDI-MS technology that can detect compounds in a tissue section without extraction, purification, separation, or labeling. MALDI-MSI can be used to visualize the spatial distribution of chemical compounds or biomolecules in foods. Although the methodology of MALDI-MSI in food science is not yet fully established, the versatility of MALDI-MSI is expected to open a new frontier in food science. Herein, we describe the principles and applications of MALDI-MSI in food science and related fields. (C) 2016 Elsevier Ltd. All rights reserved. - Shinichi Matsumura; Kazuya Murata; Nobuhiro Zaima; Yuri Yoshioka; Masanori Morimoto; Hideaki Matsuda; Masahiro IwakiNATURAL PRODUCT COMMUNICATIONS NATURAL PRODUCTS INC 11 (11) 1671 - 1674 1934-578X 2016/11 [Refereed]
The need for a preventive agent against dementia led us to screen natural plant resources. Among the herbs and spices tested, sesame seed prepared from Sesamum indicum seeds showed potent beta-secretase inhibitory activity. The active principles were determined to be sesamin and sesamolin, typical lignans in S. indicum. The IC50 values of sesamin and sesamolin were 257 and 140 mu M, respectively. These compounds were investigated in a preliminary absorption experiment. After oral administration, these compounds were detected in an intact form in the brain and serum. These results suggest that consumption of sesame seeds may prevent dementia by sesamin and sesamolin, the constituents in sesame seeds. - Teruyoshi Tanaka; Yukihiro Yokota; Hanjun Tang; Nobuhiro Zaima; Tatsuya Moriyama; Yukio KawamuraJOURNAL OF NUTRITIONAL SCIENCE AND VITAMINOLOGY CENTER ACADEMIC PUBL JAPAN 62 (5) 341 - 349 0301-4800 2016/10 [Refereed]
Postmenopausal diabetes is exacerbated by estrogen deficiency. Ovariectomized (OVX) animal models can be used to develop strategies for preventing or treating postmenopausal symptoms. We previously found that a diet containing kudzu (Pueraria lobata) vine ethanol extract (PVEE) suppressed weight gain in OVX mice. Therefore, this study further elucidated how PVEE affected OVX mice. Ten-week-old OVX or sham-operated mice were fed diets containing either no PVEE (control) or 20 mg.kg(-1).d(-1) PVEE for 8 wk, 5 mg.kg(-1).d(-1) PVEE for 24 wk, or 20 mg.kg(-1).d(-1) puerarin (daidzein-8-C-glucoside), a major isoflavone present in PVEE, for 10 wk. The effects of puerarin on glucose tolerance were also tested in OVX mice. The experimental diets were not associated with any abnormalities in any mice tested in the present study. Weight gain and serum glucose levels were increased in OVX mice and these effects were significantly attenuated in OVX mice that consumed PVEE (5 or 20 mg.kg(-1).d(-1)) or puerarin. Puerarin-treated OVX mice also showed reduced serum glucose levels following administration of 1,000 mg.kg(-1) glucose. These results suggested that puerarin contributed to PVEE-mediated improvements in glucose metabolism in OVX mice. Although further studies are needed to clarify the molecular mechanism underlying these observations, PVEE and puerarin could provide effective approaches to the amelioration of postmenopausal diabetes. - Nobuhiro Zaima; Saori Kinoshita; Nao Hieda; Hirona Kugo; Kaori Narisawa; Ayami Yamamoto; Kenichi Yanagimoto; Tatsuya MoriyamaBiochemistry and Biophysics Reports Elsevier B.V. 7 259 - 265 2405-5808 2016/09 [Refereed]
Low levels of serum testosterone are characteristically associated with diabetes, coronary atherosclerosis, obstructive sleep apnea, rheumatoid arthritis, and chronic obstructive pulmonary disease. Testosterone replacement therapy is effective against many of these disorders, indicating the importance of maintaining a healthy testosterone level. In this study, we investigated the effects of fish oil on murine testosterone metabolism and analyzed the dynamics of relevant lipids in testes by matrix-assisted laser desorption ionization mass spectrometry imaging. Testosterone was upregulated in mice that received fish oil. In the testicular interstitium, eicosapentaenoic acid-containing phosphatidylcholine was distributed characteristically. These data suggest that eicosapentaenoic acid is involved in testosterone metabolism. - Kazuko Iwamoto; Youichi Fukuda; Chisato Tokikura; Mayuko Noda; Ayami Yamamoto; Misato Yamamoto; Mitsuaki Yamashita; Nobuhiro Zaima; Akira Iida; Tatsuya MoriyamaBIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS ACADEMIC PRESS INC ELSEVIER SCIENCE 478 (3) 1136 - 1140 0006-291X 2016/09 [Refereed]
Estrogen deficiency-induced obesity has a high risk of visceral fat accumulation and body weight gain. It is also associated with many adverse health conditions. Taheebo extract from Tabebuia avellanedae has been recognized as playing several biological and pharmacological roles. Therefore, we investigated whether the intake of n-BuOH extract of Taheebo shows anti-obesity effect in ovariectomized (OVX) mice. After 16 weeks of feeding, the mice administrated with 0.5% n-BuOH extract of Taheebo showed significantly decreased body weight compared with that of the control mice, and the fat mass also showed a significant decrease. In 3T3-L1 cells, supplementation with n-BuOH extract of Taheebo significantly reduced the triglyceride ( TG) levels. Furthermore, bioassay-guided purification of the nBuOH extract based on the TG levels in 3T3-L1 cells led to the isolation of compound 2 ( 1-dehydroxy-3,4-dihydroaucubigenin). These results suggested that the anti obesity effect of Taheebo extract is due to its capability in preventing the accumulation of adipocyte in mice. Taheebo extract might be a promising functional food resources capable of protecting against OVX-induced obesity. (C) 2016 Elsevier Inc. All rights reserved. - Hirona Kugo; Nobuhiro Zaima; Hiroki Tanaka; Youhei Mouri; Kenichi Yanagimoto; Kohsuke Hayamizu; Keisuke Hashimoto; Takeshi Sasaki; Masaki Sano; Tatsuro Yata; Tetsumei Urano; Mitsutoshi Setou; Naoki Unno; Tatsuya MoriyamaScientific Reports NATURE PUBLISHING GROUP 6 31268 2045-2322 2016/08 [Refereed]
Abdominal aortic aneurysm (AAA) is a vascular disease involving the gradual dilation of the abdominal aorta. It has been reported that development of AAA is associated with inflammation of the vascular wall; however, the mechanism of AAA rupture is not fully understood. In this study, we investigated the mechanism underlying AAA rupture using a hypoperfusion-induced animal model. We found that the administration of triolein increased the AAA rupture rate in the animal model and that the number of adipocytes was increased in ruptured vascular walls compared to non-ruptured walls. In the ruptured group, macrophage infiltration and the protein levels of matrix metalloproteinases 2 and 9 were increased in the areas around adipocytes, while collagen-positive areas were decreased in the areas with adipocytes compared to those without adipocytes. The administration of fish oil, which suppresses adipocyte hypertrophy, decreased the number and size of adipocytes, as well as decreased the risk of AAA rupture ratio by 0.23 compared to the triolein administered group. In human AAA samples, the amount of triglyceride in the adventitia was correlated with the diameter of the AAA. These results suggest that AAA rupture is related to the abnormal appearance of adipocytes in the vascular wall. - Shinichi Matsumura; Kazuya Murata; Nobuhiro Zaima; Yuri Yoshioka; Masanori Morimoto; Hideaki Matsuda; Masahiro Iwaki; Masahiro IwakiNatural Product Communications 11 1671 - 1674 1934-578X 2016/01The need for a preventive agent against dementia led us to screen natural plant resources. Among the herbs and spices tested, sesame seed prepared from Sesamum indicum seeds showed potent β-secretase inhibitory activity. The active principles were determined to be sesamin and sesamolin, typical lignans in S. indicum. The IC 50 values of sesamin and sesamolin were 257 and 140 μM, respectively. These compounds were investigated in a preliminary absorption experiment. After oral administration, these compounds were detected in an intact form in the brain and serum. These results suggest that consumption of sesame seeds may prevent dementia by sesamin and sesamolin, the constituents in sesame seeds.
- Shinichi Matsumura; Kazuya Murata; Nobuhiro Zaima; Yuri Yoshioka; Masanori Morimoto; Hirona Kugo; Ayami Yamamoto; Tatsuya Moriyama; Hideaki MatsudaNatural Product Communications 11 1785 - 1788 1934-578X 2016/01The need for a preventive agent against dementia led us to screen natural plant resources. Among the herbs and spices tested, turmeric, from rhizomes of Curcuma longa, showed high potency against β-secretase. The active principles were determined as α-turmerone, β-turmerone and ar-turmerone, with IC 50 values of 39, 62 and 92 μM respectively. In this study, the efficiency of collecting the essential oil using steam distillation of the volatile substance was disclosed. The active principles were explored, and four sesquiterpenoids and five monoterpenoids were revealed as active principles against β-secretase. On the other hand, α-turmerone, β-turmerone and ar-turmerone were also investigated in a pharmacokinetic absorption experiment. After oral administration, these compounds were detected in an intact form in the brain and serum. These results suggest that consumption of turmeric constituents may prevent dementia.
- Shekhar U. Kadam; N. N. Misra; Nobuhiro ZaimaRSC ADVANCES ROYAL SOC CHEMISTRY 6 (40) 33537 - 33546 2046-2069 2016 [Refereed]
Chemical imaging based on mass spectrometry is an emerging technology which has opened opportunities for fundamental research in food science. The ability to quantitatively determine the spatial distribution of several chemical entities simultaneously makes it a method of choice for chemical characterization of plant materials and foods. In this review, an overview of the ionization methods is presented, followed by a discussion of the current state of the art in mass spectrometry imaging (MSI) of relevance to practices in food research. The known applications, analytical challenges, and future research potential are highlighted. MSI has been successfully utilized to a variable degree for obtaining information about spatial distribution of a variety of molecules and metabolites in foods. It allows visualizing the spatial molecular maps without extraction, purification, separation, or labelling of foods. The method is likely to find wider adoption with developments in ionization sources and inter-laboratory collaborations. - Tanaka H; Yamamoto N; Suzuki M; Mano Y; Sano M; Zaima N; Sasaki T; Setou M; Unno NAnnals of vascular diseases 9 (4) 277 - 284 1881-641X 2016 [Refereed]
- Hiroki Tanaka; Nobuhiro Zaima; Takeshi Sasaki; Naoto Yamamoto; Kazunori Inuzuka; Masaki Sano; Hiroyuki Konno; Tetsumei Urano; Mitsutoshi Setou; Naoki UnnoJOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS JAPAN ATHEROSCLEROSIS SOC 23 (6) 673 - 680 1340-3478 2016 [Refereed]
Aim: Asymptomatic visceral artery aneurysms (VAAs) have increasingly been found, with most being either atherosclerotic VAAs or fibromuscular dysplasia (FMD)-associated VAAs. However, little is known about the pathogenesis of both diseases. We aimed to identify the differences in the distribution pattern of lipid molecules between atherosclerotic VAAs and FMD-associated VAAs. Methods: We conducted a histological study of VAAs using imaging mass spectrometry (IMS) to assess the accumulation of lipid molecules in both the aneurysmal sac and the adjacent arteries without aneurysmal changes in 17 VAA samples, which were resected during the surgery. Results: IMS revealed characteristic distributions of cholesterol ester in intima and media in the atherosclerotic VAAs, which was hardly detected in FMD-associated VAAs. However, lysophosphatidylcholine (lysoPC), a proinflammatory and proapoptotic lipid mediator, was accumulated in the medial ridge of the adventitia of FMD-associated in the aneurysmal sac, and it was also diffusely accumulated in the adjacent arteries. In contrast, lysoPC was accumulated in the area of intimal hyperplasia in atherosclerotic VAAs and the adjacent arteries. Conclusion: The distribution patterns of lipid molecules were different between the FMD-associated and atherosclerotic VAAs. The diffuse accumulation of lysoPCs in the visceral arteries may be a predisposition for the formation of FMD-associated VAAs. - Hirona Kugo; Nobuhiro Zaima; Youhei Mouri; Hiroki Tanaka; Kenichi Yanagimoto; Tetsumei Urano; Naoki Unno; Tatsuya MoriyamaBIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY TAYLOR & FRANCIS LTD 80 (6) 1186 - 1191 0916-8451 2016 [Refereed]
Abdominal aortic aneurysm (AAA) is a vascular disease involving gradual dilation of the abdominal aorta and high rupture-related mortality rates. AAA is histologically characterized by oxidative stress, chronic inflammation, and extracellular matrix degradation in the vascular wall. We previously demonstrated that aortic hypoperfusion could cause the vascular inflammation and AAA formation. However, the preventive method for hypoperfusion-induced AAA remains unknown. In this study, we evaluated the effect of fish oil on AAA development using a hypoperfusion-induced AAA animal model. Dilation of the abdominal aorta in the fish oil administration group was smaller than in the control group. Collagen destruction and oxidative stress were suppressed in the fish oil administration group than in the control group. These results suggested that fish oil could prevent the development of AAA induced by hypoperfusion. - MALDI Mass Spectrometry Imaging of Biological StructuresZaima N; Goto-Inoue N; Hayasaka TEncyclopedia of Analytical Chemistry 2015/09 [Refereed]
- Masahiro Higashi; Ken-ichi Hirano; Kazuhiro Kobayashi; Yoshihiko Ikeda; Ami Issiki; Tetsuo Otsuka; Akira Suzuki; Satoshi Yamaguchi; Nobuhiro Zaima; Seiki Hamada; Hironori Hanada; Chieko Suzuki; Hiroshi Nakamura; Hironori Nagasaka; Toshiyuki Miyata; Yoshihiro Miyamoto; Kunihisa Kobayashi; Hiroaki Naito; Tatsushi TodaINTERNATIONAL JOURNAL OF CARDIOLOGY ELSEVIER IRELAND LTD 192 30 - 32 0167-5273 2015/08 [Refereed]
- Hiroki Tanaka; Nobuhiro Zaima; Takeshi Sasaki; Masaki Sano; Naoto Yamamoto; Takaaki Saito; Kazunori Inuzuka; Takahiro Hayasaka; Naoko Goto-Inoue; Yuki Sugiura; Kohji Sato; Hirona Kugo; Tatsuya Moriyama; Hiroyuki Konno; Mitsutoshi Setou; Naoki UnnoPLOS ONE PUBLIC LIBRARY SCIENCE 10 (8) e0134386 1932-6203 2015/08 [Refereed]
The aortic wall is perfused by the adventitial vasa vasorum (VV). Tissue hypoxia has previously been observed as a manifestation of enlarged abdominal aortic aneurysms (AAAs). We sought to determine whether hypoperfusion of the adventitial VV could develop AAAs. We created a novel animal model of adventitial VV hypoperfusion with a combination of a polyurethane catheter insertion and a suture ligation of the infrarenal abdominal aorta in rats. VV hypoperfusion caused tissue hypoxia and developed infrarenal AAA, which had similar morphological and pathological characteristics to human AAA. In human AAA tissue, the adventitial VV were stenotic in both small AAAs (30-49 mm in diameter) and in large AAAs (>50 mm in diameter), with the sac tissue in these AAAs being ischemic and hypoxic. These results indicate that hypoperfusion of adventitial VV has critical effects on the development of infrarenal AAA. - Incompetent Lymph Drainage Causes Lipid Accumulation in Perivascular Tissue and Changes Vein Wall Structure.Tanaka H; Zaima N; Sasaki T; Konno H; Setou M; Unno NJap J Phlebol 26 227 - 235 2015 [Refereed]
- Hiroki Tanaka; Nobuhiro Zaima; Takeshi Sasaki; Naoto Yamamoto; Kazunori Inuzuka; Masaki Sano; Takaaki Saito; Takahiro Hayasaka; Naoko Goto-Inoue; Kohji Sato; Hirona Kugo; Tatsuya Moriyama; Hiroyuki Konno; Mitsutoshi Setou; Naoki UnnoJOURNAL OF VASCULAR RESEARCH KARGER 52 (2) 127 - 135 1018-1172 2015 [Refereed]
The pathophysiology underlying abdominal aortic aneurysms (AAAs) remains unknown. In this study, we applied imaging mass spectrometry (IMS) to analyze the pathophysiology of the aneurysmal wall. Comparisons were performed between the tissue samples from the neck and the sac of the AAA, at a single time point, in 30 patients who underwent elective surgery of their AAAs. The localization of each lipid molecule in the aortic wall was assessed by IMS. Histopathological examination and IMS revealed a characteristic distribution of triglycerides (TGs) specifically in the aneurismal adventitia of the sac. This characteristic TG distribution was derived from an ectopic appearance of adipocytes in the adventitia. Furthermore, ectopic adipocyte accumulation in the aortic wall leads to the loss of the collagen fiber network subsequent to the wall rupture. The underlying mechanism of adipocyte accumulation involves the presence of adipose-derived stem cells (ADSCs) in the aneurismal adventitia and the expression of peroxisome proliferator-activated receptor gamma 2, a master regulator of adipocyte differentiation by some ADSCs. This study reveals new, previously overlooked aspects of AAA pathology. (C) 2015 S. Karger AG, Basel - Dai Yuki; Yuki Sugiura; Nobuhiro Zaima; Hiroyasu Akatsu; Shiro Takei; Ikuko Yao; Masato Maesako; Ayae Kinoshita; Takayuki Yamamoto; Ryo Kon; Keikichi Sugiyama; Mitsutoshi SetouSCIENTIFIC REPORTS NATURE PUBLISHING GROUP 4 7130 2045-2322 2014/11 [Refereed]
Alzheimer's disease (AD) is a progressive neurodegenerative disease that is characterized by senile plaques, neurofibrillary tangles, synaptic disruption, and neuronal loss. Several studies have demonstrated decreases of docosahexaenoic acid-containing phosphatidylcholines (DHA-PCs) in the AD brain. In this study, we used matrix-assisted laser desorption/ionization imaging mass spectrometry in postmortem AD brain to show that PC molecular species containing stearate and DHA, namely PC(18:0/22:6), was selectively depleted in the gray matter of patients with AD. Moreover, in the brain regions with marked amyloid beta (A beta) deposition, the magnitude of the PC(18:0/22:6) reduction significantly correlated with disease duration. Furthermore, at the molecular level, this depletion was associated with reduced levels of the postsynaptic protein PSD-95 but not the presynaptic protein synaptophysin. Interestingly, this reduction in PC(18:0/22:6) levels did not correlate with the degrees of A beta deposition and neuronal loss in AD. The analysis of the correlations of key factors and disease duration showed that their effects on the disease time course were arranged in order as Ab deposition, presynaptic disruption, postsynaptic disruption coupled with PC(18:0/22:6) reduction, and neuronal loss. - Nobuhiro Zaima; Sayaka Yoshioka; Yayoi Sato; Saki Shinano; Yoshihiko Ikeda; Tatsuya MoriyamaRAPID COMMUNICATIONS IN MASS SPECTROMETRY WILEY-BLACKWELL 28 (13) 1453 - 1458 0951-4198 2014/07 [Refereed]
RATIONALEVisualization of the spatial distribution of phosphatidylcholine (PC) in tissues by matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) provides insights into key physiological and pathophysiological processes. In MALDI-IMS analysis, the heterogeneity of adduct ions formed from PC lowers the specificity of detection of PC molecular species and poses a challenge in the identification of these species. To solve this problem, modified matrix solution and desalting with ammonium acetate (NH4Ac) buffer have been employed. However, the utility of these methods is limited to the analysis of brain sections. METHODSThe MALDI signal intensities of [PC+H], [PC+Na] and [PC+K] were compared after three different pretreatments (modified matrix solution, desalting with 150mM ammonium acetate, treatment with 150mM potassium acetate). RESULTSPretreatment of tissue sections with 150mM potassium acetate resulted in an increase in the signal intensity of [PC+K] ions produced from cryosections of the pancreas, brain, and liver tissues. CONCLUSIONSPretreatment with potassium acetate can be a simple, improved, and highly useful method for the reliable analysis of PC in tissues. Copyright (c) 2014 John Wiley & Sons, Ltd. - Nobuhiro Zaima; Yukihiro Yoshimura; Yukio Kawamura; Tatsuya MoriyamaRAPID COMMUNICATIONS IN MASS SPECTROMETRY WILEY-BLACKWELL 28 (13) 1515 - 1520 0951-4198 2014/07 [Refereed]
RATIONALESake is made from fermented rice and has been drunk in Japan for more than 1000 years. The rice must be polished prior to fermentation to obtain high-quality sake. It is traditionally recognized that the quality of sake is improved as the rice polishing ratio (percentage removed in the polishing process) increases. However, the underlying chemistry of the rice polishing process is incompletely understood. Herein, we analyzed the distribution of lysophosphatidylcholine (LPC) molecular species with unsaturated fatty acids in rice, as their presence is thought to exert a negative effect on the flavor of sake. METHODSThe distribution of LPC molecular species in rice was visualized via matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). RESULTSLPC (16:0) is ubiquitously present in the endosperm of rice while LPC (18:0) is localized in the core of the endosperm. In contrast, LPC (18:2) and LPC (18:1) are present in the outer region of the endosperm. CONCLUSIONSThe enhancement of the quality of sake as the polishing ratio of the rice increases might be explained in terms of the distribution of LPC with unsaturated fatty acids in the rice. Copyright (c) 2014 John Wiley & Sons, Ltd. - Yoshihiko Ikeda; Nobuhiro Zaima; Ken-ichi Hirano; Masayuki Mano; Kunihisa Kobayashi; Sohsuke Yamada; Satoshi Yamaguchi; Akira Suzuki; Hideaki Kanzaki; Toshimitsu Hamasaki; Jun-ichi Kotani; Seiya Kato; Hironori Nagasaka; Mitsutoshi Setou; Hatsue Ishibashi-UedaPATHOLOGY INTERNATIONAL WILEY-BLACKWELL 64 (7) 325 - 335 1320-5463 2014/07 [Refereed]
It is of importance to clarify pathophysiology of diabetic heart diseases such as heart failure and coronary artery disease. We reported a novel clinical phenotype called triglyceride deposit cardiomyovasculopathy (TGCV), showing aberrant TG accumulation in both coronary arteries and myocardium, in a cardiac transplant recipient. Here, we examined autopsied diabetics for TG deposition in cardiovasculature. Consecutive series of hearts from advanced diabetes mellitus (DM) subjects (DM group: DMG, n = 20) and those from age- and sex-matched non-diabetic controls (non DM group: NDMG, n = 20) were examined. The diagnostic criteria of advanced DM' was made based on 2014 Clinical Practice Recommendations proposed by the American Diabetes Association. The mean duration of DM was 15.8 years. All DMG suffered from heart diseases including coronary artery diseases and 14 subjects had multi-vessel disease. Tissue TG contents were measured biochemically. Coronary arterial TG contents was significantly higher in DMG compared with NDMG. Spatial distribution of TG in transverse sections of coronary arteries showed TG deposition mainly in smooth muscle cells by Imaging Mass Spectrometry. Abundant TG deposition in coronary artery might be associated with advanced DM. - Teruyoshi Tanaka; Kenji Takahashi; Kohsuke Adachi; Haruki Ohta; Yukihiro Yoshimura; Yasuo Agawa; Yoshifumi Sawada; Osamu Takaoka; Amal Kumar Biswas; Kenji Takii; Nobuhiro Zaima; Tatsuya Moriyama; Yukio KawamuraFISHERIES SCIENCE SPRINGER JAPAN KK 80 (3) 603 - 612 0919-9268 2014/05 [Refereed]
Type I collagen is widely distributed in most organs in teleosts. It plays a role not only in intercellular adhesion, but also in molecular signaling. In this study, Pacific bluefin tuna (PBT) procollagen alpha 1 (I) cDNA was cloned and characterized. The nine fragments of a procollagen alpha 1 (I) chain cDNA clone were prepared and spliced together to create the complete coding region. The resulting amino acid sequence was homologous with that of other teleosts. The mRNA expression profile of PBT procollagen alpha 1 (I) in various tissues and the phylogenetic analysis with other vertebrate procollagen alpha 1 (I) chains suggest that PBT procollagen alpha 1 (I) could be a precursor form of the PBT type I collagen alpha 1 chain. In addition, its level of expression in PBT larvae and early juveniles gradually increased with somatic growth. This increase was related to the standard length, wet body weight, and protein content of each individual fish. Therefore, the expression profile of procollagen alpha 1 (I) may be a useful indicator for somatic growth in fish larvae and juveniles. - Masaki Sano; Takeshi Sasaki; Satoshi Hirakawa; Junichi Sakabe; Mikako Ogawa; Satoshi Baba; Nobuhiro Zaima; Hiroki Tanaka; Kazunori Inuzuka; Naoto Yamamoto; Mitsutoshi Setou; Kohji Sato; Hiroyuki Konno; Naoki UnnoPLOS ONE PUBLIC LIBRARY SCIENCE 9 (3) 1932-6203 2014/03The pathogenesis of abdominal aortic aneurysm (AAA) is characterized to be inflammation-associated degeneration of vascular wall. Neovascularization is regularly found in human AAA and considered to play critical roles in the development and rupture of AAA. However, little is known about lymphangiogenesis in AAA. The purpose of this study was to demonstrate both angiogenesis and lymphangiogenesis in AAA. Abdominal aortic tissue was harvested either from autopsy (control group) and during open-repair surgery for AAA (AAA group). Adventitial lymphatic vasa vasorum was observed in both groups, but seemed to be no significant morphological changes in AAA. Immunohistochemical studies identified infiltration of lymphatic vessel endothelial hyaluronan receptor (LYVE) -1, vascular endothelial growth factor (VEGF)-C, and matrix metalloproteinase (MMP)-9-positive macrophages and podoplanin and Prox-1-positive microvessels in the intima/media in AAA wall, where hypoxia-inducible factors (HIF)-1 alpha was expressed. VEGF-C and MMP-9 were not expressed in macrophages infiltrating in the adventitia. Intraoperative indocyanine green fluorescence lymphography revealed lymph stasis in intima/medial in AAA. Fluorescence microscopy of the collected samples also confirmed the accumulation of lymph in the intima/media but not in adventitia. These results demonstrate that infiltration of macrophages in intima/media is associated with lymphangiogenesis and angiogenesis in AAA. Lymph-drainage appeared to be insufficient in the AAA wall.
- Ken-ichi Hirano; Tatsuya Tanaka; Yoshihiko Ikeda; Satoshi Yamaguchi; Nobuhiro Zaima; Kazuhiro Kobayashi; Akira Suzuki; Yasuhiko Sakata; Yasushi Sakata; Kunihisa Kobayashi; Tatsushi Toda; Norihide Fukushima; Hatsue Ishibashi-Ueda; Daniela Tavian; Hironori Nagasaka; Shu-Ping Hui; Hitoshi Chiba; Yoshiki Sawa; Masatsugu HoriBIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS ACADEMIC PRESS INC ELSEVIER SCIENCE 443 (2) 574 - 579 0006-291X 2014/01Adipose triglyceride lipase (ATGL, also known as PNPLA2) is an essential molecule for hydrolysis of intracellular triglyceride (TG). Genetic ATGL deficiency is a rare multi-systemic neutral lipid storage disease. Information regarding its clinical profile and pathophysiology, particularly for cardiac involvement, is still very limited. A previous middle-aged ATGL-deficient patient in our institute (Case 1) with severe heart failure required cardiac transplantation (CTx) and exhibited a novel phenotype, "Triglyceride deposit cardiomyovasculopathy (TGCV)". Here, we tried to elucidate molecular mechanism underlying TGCV. The subjects were two cases with TGCV, including our second case who was a 33-year-old male patient (Case 2) with congestive heart failure requiring CTx. Case 2 was homozygous for a point mutation in the 5' splice donor site of intron 5 in the ATGL, which results in at least two types of mRNAs due to splicing defects. The myocardium of both patients (Cases 1 and 2) showed up-regulation of peroxisome proliferated activated receptors (PPARs), key transcription factors for metabolism of long chain fatty acids (LCFAs), which was in contrast to these molecules' lower expression in ATGL-targeted mice. We investigated the intracellular metabolism of LCFAs under human ATGL-deficient conditions using patients' passaged skin fibroblasts as a model. ATGL-deficient cells showed higher uptake and abnormal intracellular transport of LCFA, resulting in massive TG accumulation. We used these findings from cardiac specimens and cell-biological experiments to construct a hypothetical model to clarify the pathophysiology of the human disorder. In patients with TGCV, even when hydrolysis of intracellular TG is defective, the marked up-regulation of PPAR gamma and related.genes may lead to increased uptake of LCFAs, the substrates for TG synthesis. This potentially vicious cycle of LCFAs could explain the massive accumulation of TG and severe clinical course for this rare disease. (C) 2013 Elsevier Inc. All rights reserved.
- Nobuhiro Zairna; Naoko Goto-Inoue; Tatsuya MoriyamaJOURNAL OF VASCULAR RESEARCH KARGER 51 (2) 144 - 148 1018-1172 2014 [Refereed]
The use of matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) for the assessment of vascular pathology is attracting attention as a new valuable tool for diagnosing disease and finding new markers. MALDI-IMS is a molecular imaging technique whereby the simultaneous measurement of multiple samples directly from clinical tissue sections is possible. The versatility of MALDI-IMS has opened a new frontier in vascular pathology. In this review, we describe the principle and applications of MALDI-IMS. (C) 2014 S. Karger AG, Basel - Hiroki Tanaka; Nobuhiro Zaima; Hideki Ito; Katsuji Hattori; Naoto Yamamoto; Hiroyuki Konno; Mitsutoshi Setou; Naoki UnnoJOURNAL OF VASCULAR SURGERY MOSBY-ELSEVIER 58 (5) 1366 - 1374 0741-5214 2013/11Objective: Triglyceride (TG) accumulation in arterial tissue is associated with the development of cardiovascular disease; however, the underlying mechanism remains unclear. Cilostazol (CLZ), a selective inhibitor of phosphodiesterase 3, has antiplatelet and vasodilating effects and may decrease serum TG levels. We examined the effect of CLZ on TG accumulation in the arterial tissue of a rat model of carotid artery ligation. Methods: Rats were fed normal chow with 0.1% CLZ (CLZ group) or without CLZ (control group) for 4 weeks after unilateral carotid artery ligation near the carotid bifurcation. Results: At the end of this period, the control group showed 3.3-fold higher TG levels in the ligated carotid artery than in the contralateral artery; however, compared with the contralateral artery, the ligated artery in the CLZ group showed significantly lower levels of TG accumulation but similar serum levels of TG, total cholesterol, and high-density lipoprotein cholesterol. Furthermore, matrix-assisted laser desorption/ionization imaging mass spectrometry revealed that the ligated carotid artery in both groups had ubiquitous accumulation of TG in the intima, media, and adventitia, along with decreased heme B signals, which was indicative of ischemia. However, heme B signals were less reduced in the CLZ group than in the control group. Conclusions: Our results indicate that CLZ can inhibit the ubiquitous accumulation of TG in arterial tissues, possibly by ameliorating tissue ischemia. CLZ may be useful in improving arterial tissue hemodynamics and lipid metabolism.
- Yukihiro Yoshimura; Saori Nishii; Nobuhiro Zaima; Tatsuya Moriyarha; Yukio KawamuraBIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS ACADEMIC PRESS INC ELSEVIER SCIENCE 434 (3) 486 - 491 0006-291X 2013/05 [Refereed]
Ellagic acid (EA) is a polyphenol found in a wide variety of plant foods that not only exhibits free radicalscavenging activity, but also confers protective effects against liver injury. Previously, we reported that pomegranate fruit extract (PFE) had an inhibitory effect on resistin secretion from differentiated murine 3T3-L1 adipocytes and identified EA contained in PFE as a potent suppressor of resistin secretion. Resistin, an adipocytokine, is considered the link between obesity and type 2 diabetes. In this study, we explored whether EA supplementation reduces serum resistin and improves hepatic steatosis and serum lipid profile by using KK-A(y) mice fed high-fat diet as a model for obese type 2 diabetes. We found that EA supplementation improved serum lipid profile and hepatic steatosis, and reduced serum resistin levels without altering mRNA expression levels in adipose tissue. Moreover, EA supplementation' upregulated mRNA expression of apoa1, ldlr, cpt1a, and ppara genes in the liver. In conclusion, our findings indicate that EA is a potent suppressor of resistin secretion in vivo and a transcriptional activator of ppara in the liver, suggesting a possibility for improving obesity-induced dyslipidemia and hepatic steatosis in KK-A(y) mice. (C) 2013 Elsevier Inc. All rights reserved. - Hiroki Tanaka; Nobuhiro Zaima; Takeshi Sasaki; Takahiro Hayasaka; Naoko Goto-Inoue; Kenji Onoue; Koji Ikegami; Yoshifumi Morita; Naoto Yamamoto; Yuuki Mano; Masaki Sano; Takaaki Saito; Kohji Sato; Hiroyuki Konno; Mitsutoshi Setou; Naoki UnnoPLoS ONE 8 (2) 1932-6203 2013/02 [Refereed]
Abdominal aortic aneurysm (AAA) is a common disease among elderly individuals. However, the precise pathophysiology of AAA remains unknown. In AAA, an intraluminal thrombus prevents luminal perfusion of oxygen, allowing only the adventitial vaso vasorum (VV) to deliver oxygen and nutrients to the aortic wall. In this study, we examined changes in the adventitial VV wall in AAA to clarify the histopathological mechanisms underlying AAA. We found marked intimal hyperplasia of the adventitial VV in the AAA sac further, immunohistological studies revealed proliferation of smooth muscle cells, which caused luminal stenosis of the VV. We also found decreased HemeB signals in the aortic wall of the sac as compared with those in the aortic wall of the neck region in AAA. The stenosis of adventitial VV in the AAA sac and the malperfusion of the aortic wall observed in the present study are new aspects of AAA pathology that are expected to enhance our understanding of this disease. © 2013 Tanaka et al. - Tatsuya Moriyama; Erika Yano; Yuusuke Suemori; Kyoko Nakano; Nobuhiro Zaima; Yukio KawamuraJournal of Nutritional Science and Vitaminology 59 (5) 462 - 469 0301-4800 2013Miso paste (miso), a fermented soybean food, is popular in Japan and other Asian countries. However, the soybean is known to induce an allergenic response in some individuals. In the present study, we evaluated the allergenicity of various kinds of miso available in Japan. Total proteins were extracted from Amakuti-kome miso, Karakuti-kome miso, Mugi-miso and Mame-miso, and the protein profiles were analyzed. The major protein bands detected in the intact soybean extract were not present in any of the miso samples, which instead showed various low molecular weight protein bands of approximately 10-25 kDa. The existence levels of six major soybean allergens were determined by Western blotting using specific antibodies. We found that the allergen levels varied among miso and allergen types however, allergen levels were consistently lower in miso than in the soybean extract. We obtained similar results for IgE-ELISA experiments using serum IgE from soybean allergy patients. Taken together, these results indicate that compared to soybean extract, various types of miso contain small quantities of intact soybean allergens. Additionally, several lines of evidence indicated that the allergen levels were exceptionally low in the dark-colored Karakuti-kome miso and Mame-miso, which are produced with relatively long fermentation periods, suggesting that the duration of fermentation might be a key factor in the hypoallergenicity of miso.
- Nobuhiro Zaima; Itsuko IshizakiTocopherol: Sources, Uses and Health Benefits 35 - 43 2012/12Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and secondary ion mass spectrometry (SIMS) are powerful tools for visualization of alpha-tocopherol in biological samples. In this review, we describe the methodology and applications of imaging mass spectrometry based on MALDI-MS (MALDI-IMS) and time-of-flight SIMS (TOF-SIMS) for visualization of alpha-tocopherol in biological samples. © 2012 by Nova Science Publishers, Inc. All rights reserved.
- Nobuhiro ZaimaRice: Production, Consumption and Health Benefits 175 - 182 2012/12Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) is a two-dimensional MALDI-mass spectrometric technique used to visualize the spatial distribution of biomolecules without the need for extraction, purification, separation, or labeling of biological samples. MALDI-IMS has revealed the characteristic distribution of several biomolecules, including proteins, peptides, amino acids, lipids, carbohydrates, and nucleotides, in various tissues. The versatility of MALDI-IMS has opened a new frontier in several fields. In this review, the methodology and applications of MALDI-IMS for analysis of rice samples are described. © 2012 by Nova Science Publishers, Inc. All rights reserved.
- Naoko Goto-Inoue; Takahiro Hayasaka; Nobuhiro Zaima; Kimiko Nakajima; Walter M. Holleran; Shigetoshi Sano; Yoshikazu Uchida; Mitsutoshi SetouPLOS ONE PUBLIC LIBRARY SCIENCE 7 (11) 1932-6203 2012/11Imaging mass spectrometry (IMS) is a useful cutting edge technology used to investigate the distribution of biomolecules such as drugs and metabolites, as well as to identify molecular species in tissues and cells without labeling. To protect against excess water loss that is essential for survival in a terrestrial environment, mammalian skin possesses a competent permeability barrier in the stratum corneum (SC), the outermost layer of the epidermis. The key lipids constituting this barrier in the SC are the ceramides (Cers) comprising of a heterogeneous molecular species. Alterations in Cer composition have been reported in several skin diseases that display abnormalities in the epidermal permeability barrier function. Not only the amounts of different Cers, but also their localizations are critical for the barrier function. We have employed our new imaging system, capable of high-lateral-resolution IMS with an atmospheric-pressure ionization source, to directly visualize the distribution of Cers. Moreover, we show an ichthyotic disease pathogenesis due to abnormal Cer metabolism in Dorfman-Chanarin syndrome, a neutral lipid storage disorder with ichthyosis in human skin, demonstrating that IMS is a novel diagnostic approach for assessing lipid abnormalities in clinical setting, as well as for investigating physiological roles of lipids in cells/tissues.
- Teruyoshi Tanaka; Kenji Takahashi; Naoki Iwamoto; Yasuo Agawa; Yoshifumi Sawada; Yukihiro Yoshimura; Nobuhiro Zaima; Tatsuya Moriyama; Yukio KawamuraFISHERIES SCIENCE SPRINGER TOKYO 78 (4) 911 - 921 0919-9268 2012/07We have shown that dietary bluefin tuna skin (TUS) protects against carbon tetrachloride (CCl4)-induced hepatic damage in mice. The CCl4-induced necrotic area was decreased in mice fed a TUS-containing diet. Consistent with the decreased necrotic area, dietary TUS markedly lowered the elevated serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and the thiobarbituric acid-reactive substance (TBARS) formation induced by CCl4 injection. TUS diets also decreased phosphorylation of inhibitory kappa B-alpha and blocked the translocation of nuclear factor-kappa B to the nucleus. TUS is composed mainly (80.7 %) of type I collagen, and our results revealed that dietary tuna collagen peptides (TUCP) attenuated the increased hepatic necrotic area, serum AST and ALT activities, and liver TBARS levels induced by CCl4, similar to TUS, thus enabling us to attribute the hepatoprotective action of TUS in CCl4-intoxicated mice to tuna collagen. Therefore, TUS and TUCP may be potential food resources that are capable of alleviating hepatitis symptoms.
- Yuki Sugiura; Nobuhiro Zaima; Mitsutoshi Setou; Seiji Ito; Ikuko YaoANALYTICAL AND BIOANALYTICAL CHEMISTRY SPRINGER HEIDELBERG 403 (7) 1851 - 1861 1618-2642 2012/06Metabolite distribution imaging via imaging mass spectrometry (IMS) is an increasingly utilized tool in the field of neurochemistry. As most previous IMS studies analyzed the relative abundances of larger metabolite species, it is important to expand its application to smaller molecules, such as neurotransmitters. This study aimed to develop an IMS application to visualize neurotransmitter distribution in central nervous system tissue sections. Here, we raise two technical problems that must be resolved to achieve neurotransmitter imaging: (1) the lower concentrations of bioactive molecules, compared with those of membrane lipids, require higher sensitivity and/or signal-to-noise (S/N) ratios in signal detection, and (2) the molecular turnover of the neurotransmitters is rapid; thus, tissue preparation procedures should be performed carefully to minimize postmortem changes. We first evaluated intrinsic sensitivity and matrix interference using Matrix Assisted Laser Desorption/Ionization (MALDI) mass spectrometry (MS) to detect six neurotransmitters and chose acetylcholine (ACh) as a model for study. Next, we examined both single MS imaging and MS/MS imaging for ACh and found that via an ion transition from m/z 146 to m/z 87 in MS/MS imaging, ACh could be visualized with a high S/N ratio. Furthermore, we found that in situ freezing method of brain samples improved IMS data quality in terms of the number of effective pixels and the image contrast (i.e., the sensitivity and dynamic range). Therefore, by addressing the aforementioned problems, we demonstrated the tissue distribution of ACh, the most suitable molecular specimen for positive ion detection by IMS, to reveal its localization in central nervous system tissues.
- Yukihiro Yoshimura; Hirofumi Enomoto; Tatsuya Moriyama; Yukio Kawamura; Mitsutoshi Setou; Nobuhiro ZaimaANALYTICAL AND BIOANALYTICAL CHEMISTRY SPRINGER HEIDELBERG 403 (7) 1885 - 1895 1618-2642 2012/06 [Refereed]
Anthocyanins are naturally occurring compounds that impart color to fruits, vegetables, and plants, and are believed to have a number of beneficial health effects in both humans and animals. Because of these properties, pharmacokinetic analysis of anthocyanins in tissue has been performed to quantify and identify anthocyanin species although, currently, no methods exist for investigating tissue localization of anthocyanin species or for elucidating the mechanisms of anthocyanin activity. Imaging mass spectrometry (IMS) is powerful tool for determining and visualizing the distribution of a wide range of biomolecules. To investigate whether anthocyanin species could be identified and visualized by IMS, we performed matrix-assisted laser desorption/ionization (MALDI)-IMS analysis, by tandem mass spectrometry (MALDI-IMS-MS), of ten anthocyanin molecular species in rabbiteye blueberry (Vaccinium ashei). The distribution patterns of each anthocyanin species were different in the exocarp and endocarp of blueberry sections. Anthocyanin species composed of delphinidin and petunidin were localized mainly in the exocarp. In contrast, those species composed of cyanidin, peonidin, and malvidin were localized in both the exocarp and the endocarp. Moreover, MALDI-IMS analysis of anthocyanidins in a blueberry section indicated that the distribution patterns of each anthocyanidin species were nearly identical with those of the corresponding anthocyanins. These results suggested that the different distribution patterns of anthocyanin species in the exocarp and endocarp depended on the aglycone rather than on the sugar moieties. This study is the first to visualize anthocyanin molecular species in fruits. - Naoko Goto-Inoue; Takahiro Hayasaka; Nobuhiro Zaima; Mitsutoshi SetouSURFACE AND INTERFACE ANALYSIS WILEY-BLACKWELL 44 (6) 749 - 754 0142-2421 2012/06Although lipid metabolism is thought to be important for proper testicular maturation, the molecular mechanisms underlying this dynamic process remain incompletely understood. Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) can generate molecular ion images of tissue surfaces with high sensitivities and minimal chemical damage. With a wide range of detectable targets, we visualized various kinds of metabolites, such as glutathione, UDP-HexNAc, phosphatidylcholine, sphingomyelin, phosphatidylinositol, seminolipid, and sulfatide. Here, we demonstrate the use of MALDI-IMS with frozen sections of mouse testis at different developmental stages and clearly reveal that some molecular species of phosphatidylcholines and seminolipids show stage-specific expression in testis. The result suggested that these molecular species serve different cellular functions during maturation. Copyright (c) 2011 John Wiley & Sons, Ltd.
- Kohsuke Adachi; Kana Fukumorita; Michihiro Araki; Nobuhiro Zaima; Zhi-Hong Yang; Satoru Chiba; Hideki Kishimura; Hiroki SaekiJOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY AMER CHEMICAL SOC 60 (22) 5540 - 5546 0021-8561 2012/06Trypsin inhibitors (TIs) have various nutritional effects. However, a detailed mechanism for their effects, especially on the gene expression patterns in various tissues, remains unknown. Here, we used transcriptome techniques and gene ontology (GO) analysis to examine the effects of squid TI (sqTI), a biochemically stable peptide, on diabetic Goto-Kakizaki rats after feeding for 10 weeks. We demonstrated that downregulation of SREBP1c in the liver via duodenal/pancreatic hormones suppresses the blood cholesterol level. Consistently, in GO analysis, the term "cholesterol biosynthetic process" was enriched among downregulated genes. No hypoglycemic or insulinotropic effects were observed, in contrast to the results from our previous studies (single stimulation with the same dose of TI), which can be partly ascribed to the inactive responses of the duodenum and pancreas in this condition.
- Hiroki Tanaka; Nobuhiro Zaima; Takeshi Sasaki; Naoto Yamamoto; Masaki Sano; Hiroyuki Konno; Mitsutoshi Setou; Naoki UnnoJOURNAL OF VASCULAR SURGERY MOSBY-ELSEVIER 55 (5) 1440 - 1448 0741-5214 2012/05Objective: Recent studies suggest that biologic changes in the vein wall associated with varicose veins (VVs) occur not only in valvular tissue but also in nonvalvular regions. We previously used imaging mass spectrometry (IMS) to determine the distribution of lipid molecules in incompetent valve tissue. In this study, we used IMS to analyze incompetent great saphenous veins (GSVs) in patients with varicose vein (VV) to assess the distribution of lipid molecules. Methods: We obtained GSV tissue from 38 VV patients (50 limbs) who underwent GSV stripping. For the control veins (CV), we obtained GSV samples from 10 patients undergoing infrainguinal bypass with reversed GSV grafting for peripheral artery occlusive disease (10 limbs). Conventional and immunofluorescence staining were performed for histopathologic examination. The total lipid content in the homogenized vein tissue was determined. The localization of each lipid molecule in the vein wall was assessed by IMS. Results: The histologic examination showed the VV walls were significantly thicker than the CV walls, and only the VV adventitia was positive for lipid staining. The VV wall had higher concentrations of phospholipids and triglycerides than the CV wall. IMS revealed an abnormal accumulation of lysophosphatidylcholine (LPC; 1-acyl 16:0) and phosphatidylcholine (diacyl 16:0/20:4) in the VV intima and media. Triglyceride was found only in VV adventitia. The number of lymphatic vessels, as measured by staining with D2-40, a lymphatic vessel-specific marker, was significantly lower in the VV adventitia than in the CV adventitia. Lymphatic vessel reduction may be associated with insufficient lymphatic drainage in the VV adventitia causing histologic changes in VV tissue. Conclusions: The accumulation of LPC(1-acyl 16: 0) and PC(diacyl 16:0/20: 4) in the VV intima and media may be associated with chronic inflammation, leading to VV tissue degeneration. Furthermore, insufficient lipid drainage by lymphatic vessel may be responsible for accumulation of lipid molecules and subsequent vein wall degeneration. (J Vasc Surg 2012;55:1440-8.)
- 2型糖尿病関連中性脂肪蓄積心筋血管症平野 賢一; 池田 善彦; 財満 信宏; 眞能 正幸; 小林 邦久; 神崎 秀明; 加藤 誠也; 笹栗 靖之; 友池 仁暢; 瀬藤 光利; 植田 初江日本病理学会会誌 (一社)日本病理学会 101 (1) 283 - 283 0300-9181 2012/03
- ヒト頸動脈と動脈硬化性プラークのメタボロミクス武藤 清佳; 植田 初江; 飯原 弘二; 山本 卓志; 財満 信宏; 松山 高明; 池田 善彦; 池川 雅哉日本病理学会会誌 (一社)日本病理学会 101 (1) 399 - 399 0300-9181 2012/03
- Piyachat Chansela; Naoko Goto-Inoue; Nobuhiro Zaima; Morakot Sroyraya; Prasert Sobhon; Mitsutoshi SetouPEPTIDES ELSEVIER SCIENCE INC 34 (1) 10 - 18 0196-9781 2012/03The distributions of neuropeptides in paraffin-embedded tissue sections (PETS) of the eyestalk, brain, and thoracic ganglia of the shrimp Penaeus monodon were visualized by imaging mass spectrometry (IMS). Peptide signals were obtained from PETS without affecting morphological features. Twenty-nine neuropeptides comprising members of FMRFamide, SIFamides, crustacean hyperglycaemic hormone, orcokinin-related peptides, tachykinin-related peptides, and allatostatin A were detected and visualized. Among these findings we first identified tachykinin-related peptide as a novel neuropeptide in this shrimp species. We found that these neuropeptides were distributed at specific areas in the three neural organs. In addition, 28 peptide sequences derived from 4 types of constitutive proteins, including actin, histones, arginine kinase, and cyclophilin A were also detected. All peptide sequences were verified by liquid chromatography-tandem mass spectrometry. The use of IMS on acetic acid-treated PETS enabled us to identify peptides and obtain their specific localizations in correlation with the undisturbed histological structure of the tissue samples. (C) 2011 Elsevier Inc. All rights reserved.
- Piyachat Chansela; Naoko Goto-Inoue; Nobuhiro Zaima; Takahiro Hayasaka; Morakot Sroyraya; Napamanee Kornthong; Attakorn Engsusophon; Montakan Tamtin; Chatchawalee Chaisri; Prasert Sobhon; Mitsutoshi SetouPLOS ONE PUBLIC LIBRARY SCIENCE 7 (3) 1932-6203 2012/03Ovary maturation, oocyte differentiation, and embryonic development in shrimp are highly dependent on nutritional lipids taken up by female broodstocks. These lipids are important as energy sources as well as for cell signaling. In this study, we report on the compositions of major lipids, i.e. phosphatidylcholines (PCs), triacylglycerols (TAGs), and fatty acids (FAs), in the ovaries of the banana shrimp, Penaeus merguiensis, during ovarian maturation. Thin-layer chromatography analysis showed that the total PC and TAG signal intensities increased during ovarian maturation. Further, by using gas chromatography, we found that (1) FAs 14:0, 16:1, 18:1, 18:2, 20:1, and 22:6 proportionally increased as ovarian development progressed to more mature stages; (2) FAs 16:0, 18:0, 20:4, and 20:5 proportionally decreased; and (3) FAs 15:0, 17:0, and 20:2 remained unchanged. By using imaging mass spectrometry, we found that PC 16:0/16:1 and TAG 18:1/18:2/22:6 were detected in oocytes stages 1 and 2. PCs 16:1/20:4, 16:0/22:6, 18:3/22:6, 18:1/22:6, 20:5/22:6, and 22:6/22:6 and TAGs 16:0/16:1/18:3, 16:0/18:1/18:3, 16:0/18:1/18:1, and 16:0/18:2/22:6 were present in all stages of oocytes. In contrast, the PC-and TAG-associated FAs 20:4, 20:5, and 22:6 showed high signal intensities in stage 3 and 4 oocytes. These FAs may act as nutrition sources as well as signaling molecules for developing embryos and the hatching process. Knowledge of lipid compositions and localization could be helpful for formulating the diet for female broodstocks to promote fecundity and larval production.
- 我が国で見いだされた新規疾患単位、中性脂肪蓄積心筋血管症 希少難病からcommon diseaseへの展開平野 賢一; 財満 信宏; 池田 善彦; 眞能 正幸; 小林 邦久; 神崎 秀明; 北風 政史; 小室 一成; 瀬藤 光利; 友池 仁暢日本内科学会雑誌 (一社)日本内科学会 101 (Suppl.) 229 - 229 0021-5384 2012/02
- Yukihiro Yoshimura; Nobuhiro Zaima; Tatsuya Moriyama; Yukio KawamuraPLOS ONE PUBLIC LIBRARY SCIENCE 7 (2) 1932-6203 2012/02Black rice (Oryza sativa L. Japonica) contains high levels of anthocyanins in the pericarp and is considered an effective health-promoting food. Several studies have identified the molecular species of anthocyanins in black rice, but information about the localization of each anthocyanin species is limited because methodologies for investigating the localization such as determining specific antibodies to anthocyanin, have not yet been developed Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) is a suitable tool for investigating the localization of metabolites. In this study, we identified 7 species of anthocyanin monoglycosides and 2 species of anthocyanin diglycosides in crude extracts from black rice by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) analysis. We also analyzed black rice sections by MALDI-IMS and found 2 additional species of anthocyanin pentosides and revealed different localization patterns of anthocyanin species composed of different sugar moieties. Anthocyanin species composed of a pentose moiety (cyanidin-3-O-pentoside and petunidin-3-O-pentoside) were localized in the entire pericarp, whereas anthocyanin species composed of a hexose moiety (cyanidin-3-O-hexoside and peonidin-3-O-hexoside) were focally localized in the dorsal pericarp. These results indicate that anthocyanin species composed of different sugar moieties exhibit different localization patterns in the pericarp of black rice. This is the first detailed investigation into the localization of molecular species of anthocyanins by MALDI-IMS.
- Yasuko Makino-Wakagi; Yukihiro Yoshimura; Yuki Uzawa; Nobuhiro Zaima; Tatsuya Moriyama; Yukio KawamuraBIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS ACADEMIC PRESS INC ELSEVIER SCIENCE 417 (2) 880 - 885 0006-291X 2012/01 [Refereed]
Resistin, an adipocytokine, is considered the link between obesity and type 2 diabetes. Pomegranate is a rich source of compounds used to treat metabolic diseases including type 2 diabetes. In this study, we found that consumption of pomegranate fruit extract (PFE) predominantly reduced the serum resistin levels in ovariectomized mice, an animal model with elevated resistin levels in serum and upregulated resistin mRNA expression in white adipose tissue. Moreover, the PFE significantly reduced the secretion and intracellular protein levels of resistin in differentiated murine 3T3-L1 adipocytes, but it did not alter resistin mRNA expression. When de novo protein synthesis was inhibited by the protein synthesis inhibitor cycloheximide, the intracellular resistin protein levels were drastically reduced by the PFE, suggesting that the PFE promoted the degradation of resistin at the protein level. We also found that ellagic acid (EA), a main component of pomegranate, had the same effects on the secretion and intracellular protein level of resistin. These results suggest that EA in pomegranate suppresses resistin secretion by a novel mechanism involving the degradation of intracellular resistin protein in adipocytes. (C) 2011 Elsevier Inc. All rights reserved. - Teruyoshi Tanaka; Hanjun Tang; Fengnian Yu; Seiwa Michihara; Yuki Uzawa; Nobuhiro Zaima; Tatsuya Moriyama; Yukio KawamuraJOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY AMER CHEMICAL SOC 59 (24) 13230 - 13237 0021-8561 2011/12Bone-loss-improving action of kudzu vine ethanol extracts (PVEE) was clarified. PVEE was composed roughly of 80% fiber, 10% puerarin, 3.6% daidzin, 2.5% 6 ''-O-malonyldaidzin, and the other minor isoflavones. Ten-week-old ovariectomized (OVX) mice were fed diets containing PVEE (20 mg/kg body weight/day) for 8 weeks. The bone resorption markers (urinary deoxypyridinoline and tartrate-resistant acid phosphatase activity) was elevated in OVX mice and was significantly decreased in OVX mice that consumed PVEE for 8 weeks. Consistent with the decrease in the markers, the number of matured osteoclasts in the distal femur was diminished in OVX mice fed PVEE diets. PVEE diets also suppressed the decrease in femoral bone mineral density (BMD) by OVX. PVEE showed the affinity for estrogen receptor alpha and beta 3 nearly 1/10000 weaker than 17 beta-estradiol. No hypertrophy in the uterus by the PVEE diet was observed. These results suggest that PVEE could be a promising resource for a functional food that improves osteoporosis.
- Goto-Inoue N; Hayasaka T; Zaima N; Setou MBiochimica et biophysica acta 11 1811 (11) 961 - 969 0006-3002 2011/11 [Refereed]
- Naoko Goto-Inoue; Takahiro Hayasaka; Nobuhiro Zaima; Mitsutoshi SetouBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids 1811 (11) 961 - 969 1388-1981 2011/11Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is a powerful tool that enables the simultaneous detection and identification of biomolecules in analytes. MALDI-imaging mass spectrometry (MALDI-IMS) is a two-dimensional MALDI-MS technique used to visualize the spatial distribution of biomolecules without extraction, purification, separation, or labeling of biological samples. This technique can reveal the distribution of hundreds of ion signals in a single measurement and also helps in understanding the cellular profile of the biological system. MALDI-IMS has already revealed the characteristic distribution of several kinds of lipids in various tissues. The versatility of MALDI-IMS has opened a new frontier in several fields, especially in lipidomics. In this review, we describe the methodology and applications of MALDI-IMS to biological samples. This article is part of a Special Issue entitled: Lipodomics and Imaging Mass Spectrometry. © 2011 Elsevier B.V.
- D. Yuki; Y. Sugiura; N. Zaima; H. Akatsu; Y. Hashizume; T. Yamamoto; M. Fujiwara; K. Sugiyama; M. SetouNEUROSCIENCE PERGAMON-ELSEVIER SCIENCE LTD 193 44 - 53 0306-4522 2011/10Sulfatide (ST) is a sphingolipid with an important role in the central nervous system as a major component of the myelin sheath. ST contains a structurally variable ceramide moiety, with a fatty acid substituent of varying carbon-chain length and double-bond number. Hydroxylation at the alpha-2 carbon position of the fatty acid is found in half the population of ST molecules. Recent genetic studies of fatty acid 2-hydroxylase (FA2H) indicate that these hydroxylated sphingolipids influence myelin sheath stability. However, their distribution is unknown. Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) enables the analysis of distinct distributions of individual ST molecular species in tissue section. We examined human cerebral cortex tissue sections with MALDI-IMS, identifying and characterizing the distributions of 14 ST species. The distribution analysis reveals that the composition ratios of non-hydroxylated/hydroxylated STs are clearly reversed at the border between white and gray matter; the hydroxylated group is the dominant ST species in the gray matter. These results suggest that hydroxylated STs are highly expressed in oligodendrocytes in gray matter and might form stable myelin sheaths. As a clinical application, we analyzed a brain with Alzheimer's disease (AD) as a representative neurodegenerative disease. Although previous studies of AD pathology have reported that the amount of total ST is decreased in the cerebral cortex, as far as the compositional distributions of STs are concerned, AD brains were similar to those in control brains. In conclusion, we suggest that MALDI-IMS is a useful tool for analysis of the distributions of various STs and this application might provide novel insight in the clinical study of demyelinating diseases. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.
- Michihiko Luca Waki; Kenji Onoue; Tsukasa Takahashi; Kensuke Goto; Yusuke Saito; Katsuaki Inami; Ippei Makita; Yurika Angata; Tomomi Suzuki; Mihi Yamashita; Narumi Sato; Saki Nakamura; Dai Yuki; Yuki Sugiura; Nobuhiro Zaima; Naoko Goto-Inoue; Takahiro Hayasaka; Yutaka Shimomura; Mitsutoshi SetouPLOS ONE PUBLIC LIBRARY SCIENCE 6 (10) 1932-6203 2011/10 [Refereed]
Background: Human hair is one of the essential components that define appearance and is a useful source of samples for non-invasive biomonitoring. We describe a novel application of imaging mass spectrometry (IMS) of hair biomolecules for advanced molecular characterization and a better understanding of hair aging. As a cosmetic and biomedical application, molecules whose levels in hair altered with aging were comprehensively investigated. Methods: Human hair was collected from 15 young (20 +/- 65 years old) and 15 older (50 +/- 65 years old) volunteers. Matrix-free laser desorption/ionization IMS was used to visualize molecular distribution in the hair sections. Hair-specific ions displaying a significant difference in the intensities between the 2 age groups were extracted as candidate markers for aging. Tissue localization of the molecules and alterations in their levels in the cortex and medulla in the young and old groups were determined. Results: Among the 31 molecules detected specifically in hair sections, 2-one at m/z 153.00, tentatively assigned to be dihydrouracil, and the other at m/z 207.04, identified to be 3,4-dihydroxymandelic acid (DHMA)-exhibited a higher signal intensity in the young group than in the old, and 1 molecule at m/z 164.00, presumed to be O-phosphoethanolamine, displayed a higher intensity in the old group. Among the 3, putative O-phosphoethanolamine showed a cortex-specific distribution. The 3 molecules in cortex presented the same pattern of alteration in signal intensity with aging, whereas those in medulla did not exhibit significant alteration. Conclusion: Three molecules whose levels in hair altered with age were extracted. While they are all possible markers for aging, putative dihydrouracil and DHMA, are also suspected to play a role in maintaining hair properties and could be targets for cosmetic supplementation. Mapping of ion localization in hair by IMS is a powerful method to extract biomolecules in specified regions and determine their tissue distribution. - 質量顕微鏡法を用いた神経伝達物質の検出と可視化に向けた検討矢尾 育子; 杉浦 悠毅; 財満 信宏; 瀬藤 光利; 伊藤 誠二JSBMS Letters (一社)日本医用マススペクトル学会 36 (Suppl.) 89 - 89 1881-5464 2011/08
- Nobuhiro Zaima; Takeshi Sasaki; Hiroki Tanaka; Xian Wu Cheng; Kenji Onoue; Takahiro Hayasaka; Naoko Goto-Inoue; Hirofumi Enomoto; Naoki Unno; Masafumi Kuzuya; Mitsutoshi SetouATHEROSCLEROSIS ELSEVIER IRELAND LTD 217 (2) 427 - 432 0021-9150 2011/08 [Refereed]
Aims: Imaging mass spectrometry (IMS) enables the visualization of individual molecules present on tissue sections. We attempted to identify and visualize specific markers for aortic atherosclerotic lesions. Methods and results: Atherosclerotic lesions were obtained from aortic roots of apolipoprotein E (ApoE)deficient mice at 60 weeks of age and from femoral arteries of humans with peripheral artery occlusive disease. IMS was performed with a matrix-assisted laser desorption/ionization mass spectrometry time-of-flight (TOF)/TOF-type instrument. The molecular ions at m/z 671.6 and 673.6 were found to be specific molecules in the mouse and human lipid-rich regions. These molecules were assigned as cholesterol linoleate (CE 18:2) and cholesterol oleate (CE 18:1). In the case of the human samples, triacylglycerol was also localized in the lipid-rich regions. The distributions of the molecular ions at m/z 804.5 and 832.5 were the same as the distribution of both the mouse and the human SMCs. These molecules were assigned as phosphatidylcholine (PC) (diacyl 16: 0/20:4) and PC (diacyl 18: 0/20:4). The molecular ion at m/z 566.9 was localized in the mouse calcified regions, and the molecular ions at m/z 539.0 were localized in the human calcified regions. Conclusions: The IMS-based histopathologic examination (IbHE) revealed the characteristic peaks of lipid-rich regions, SMCs, and calcified regions in the atherosclerotic lesions. In addition, IbHE revealed the characteristic distribution of lipids in human atherosclerotic lesions. These data indicate that an IMS-based pathologic approach is of considerable value as a new histopathologic examination. (C) 2011 Elsevier Ireland Ltd. All rights reserved. - Kohsuke Adachi; Kana Fukumorita; Michihiro Araki; Nobuhiro Zaima; Satoru Chiba; Hideki Kishimura; Hiroki SaekiJOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY AMER CHEMICAL SOC 59 (16) 9001 - 9010 0021-8561 2011/08To investigate the effects of oral administration of a trypsin inhibitor (TI), normal Wistar rats were fed a TI derived from squid (Todarodes pacificus) for 10 weeks and gene expression profiles in the duodenum, pancreas, liver, and muscle were then analyzed using DNA microarrays. Although no significant changes could be observed in growth, food intake, tissue weight, or blood tests among the tissues tested, the duodenum showed the most remarkable changes in the global gene expression profile. Significant up-regulation of mRNAs encoding gastrin, gastrokine, cholecystokinin and somatostatin in the duodenum was validated by qPCR analysis. In gene ontology (GO) analysis of the up-regulated differentially expressed genes (DEGs), GO terms related to keratinization and innate mucosal defense were enriched (p < 0.001) in the category of biological processes in addition to assumable terms such as regulation of secretion and response to nutrients, vesicle-mediated transport, and so forth. In the same analysis, calcium ion binding was listed at the deepest hierarchy in the category of molecular function. These results indicate that the duodenum responds to TI treatment by a wider range of physiological processes than previously assumed such as keratinocyte differentiation and innate mucosal defense, in which calcium plays a crucial role.
- Hiroki Tanaka; Nobuhiro Zaima; Naoto Yamamoto; Minoru Suzuki; Yuuki Mano; Hiroyuki Konno; Naoki Unno; Mitsutoshi SetouANALYTICAL AND BIOANALYTICAL CHEMISTRY SPRINGER HEIDELBERG 400 (7) 1873 - 1880 1618-2642 2011/06Arteriovenous fistulae (AVF) using vein grafts are frequently used for vascular access in hemodialysis. When superficial veins are used as autogenous access grafts for hemodialysis, atherosclerotic-like tissue degeneration often causes stenosis and obstruction. Although the differences between the pathology of degeneration in AVF and atherosclerosis (i.e., peripheral artery occlusive disease (PAD)) are known, their underlying molecular mechanisms are not. We determined the characteristic abnormal lipid metabolism of AVF. Oil red O staining clearly showed the accumulation of lipid molecules in AVF and PAD tissues. We found that the staining pattern was different between AVF and PAD tissues. The media and adventitia of AVF and the intima and media of PAD were intensely stained. Quantitative lipid analysis revealed that the amount of PL was significantly increased in AVF and PAD. Next, we performed matrix-assisted laser desorption/ionization imaging mass spectroscopy and determined the characteristic distribution of lysophosphatidylcholine (LPC) and phosphatidylcholine (PC) in AVF. The distribution patterns of LPC (1-acyl 16:0) and PC (diacyl 16:0/20:4) were consistent with the Oil red O staining images, suggesting that metabolisms related to LPC (1-acyl 16:0) and PC (diacyl 16:0/20:4) are altered in AVF.
- Hirofumi Enomoto; Yuki Sugiura; Mitsutoshi Setou; Nobuhiro ZaimaANALYTICAL AND BIOANALYTICAL CHEMISTRY SPRINGER HEIDELBERG 400 (7) 1913 - 1921 1618-2642 2011/06 [Refereed]
The mammalian tongue is one of the most important organs during food uptake because it is helpful for mastication and swallowing. In addition, taste receptors are present on the surface of the tongue. Lipids are the second most abundant biomolecules after water in the tongue. Lipids such as phosphatidylcholine (PC), lysophosphatidylcholine (LPC) and sphingomyelin (SM) are considered to play fundamental roles in the mediation of cell signaling. Imaging mass spectrometry (IMS) is powerful tool for determining and visualizing the distribution of lipids across sections of dissected tissue. In this study, we identified and visualized the PC, LPC, and SM species in a mouse tongue body section with matrix-assisted laser desorption/ionization (MALDI)-IMS. The ion image constructed from the peaks revealed that docosahexaenoic acid (DHA)-containing PC, LPC, linoleic acid-containing PC and SM (d18:1/16:0), and oleic acid-containing PC were mainly distributed in muscle, connective tissue, stratified epithelium, and the peripheral nerve, respectively. Furthermore, the distribution of SM (d18:1/16:0) corresponded to the distribution of nerve tissue relating to taste in the stratified epithelium. This study represents the first visualization of PC, LPC and SM localization in the mouse tongue body. - Junya Matsumoto; Yuki Sugiura; Dai Yuki; Takahiro Hayasaka; Naoko Goto-Inoue; Nobuhiro Zaima; Yasuto Kunii; Akira Wada; Qiaohui Yang; Keisuke Nishiura; Hiroyasu Akatsu; Akira Hori; Yoshio Hashizume; Takayuki Yamamoto; Keiko Ikemoto; Mitsutoshi Setou; Shin-ichi NiwaANALYTICAL AND BIOANALYTICAL CHEMISTRY SPRINGER HEIDELBERG 400 (7) 1933 - 1943 1618-2642 2011/06Schizophrenia is one of the major psychiatric disorders, and lipids have focused on the important roles in this disorder. In fact, lipids related to various functions in the brain. Previous studies have indicated that phospholipids, particularly ones containing polyunsaturated fatty acyl residues, are deficient in postmortem brains from patients with schizophrenia. However, due to the difficulties in handling human postmortem brains, particularly the large size and complex structures of the human brain, there is little agreement regarding the qualitative and quantitative abnormalities of phospholipids in brains from patients with schizophrenia, particularly if corresponding brain regions are not used. In this study, to overcome these problems, we employed matrix-assisted laser desorption/ionization imaging mass spectrometry (IMS), enabling direct microregion analysis of phospholipids in the postmortem brain of a patient with schizophrenia via brain sections prepared on glass slides. With integration of traditional histochemical examination, we could analyze regions of interest in the brain at the micrometric level. We found abnormal phospholipid distributions within internal brain structures, namely, the frontal cortex and occipital cortex. IMS revealed abnormal distributions of phosphatidylcholine molecular species particularly in the cortical layer of frontal cortex region. In addition, the combined use of liquid chromatography/electrospray ionization tandem mass spectrometry strengthened the capability for identification of numerous lipid molecular species. Our results are expected to further elucidate various metabolic processes in the neural system.
- Nobuhiro Zaima; Naoko Goto-Inoue; Takahiro Hayasaka; Hirofumi Enomoto; Mitsutoshi SetouANALYTICAL AND BIOANALYTICAL CHEMISTRY SPRINGER HEIDELBERG 400 (7) 1865 - 1871 1618-2642 2011/06 [Refereed]
It has become necessary to assess the authenticity of beef origin because of concerns regarding human health hazards. In this study, we used a metabolomic approach involving matrix-assisted laser desorption/ionization imaging mass spectrometry to assess the authenticity of beef origin. Highly accurate data were obtained for samples of extracted lipids from beef of different origin; the samples were grouped according to their origin. The analysis of extracted lipids in this study ended within 10 min, suggesting this approach can be used as a simple authenticity assessment before a definitive identification by isotope analysis. - Norio Miyamura; Takashi Nakamura; Naoko Goto-Inoue; Nobuhiro Zaima; Takahiro Hayasaka; Tokiwa Yamasaki; Shuji Terai; Isao Sakaida; Mitsutoshi Setou; Hiroshi NishinaBIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS ACADEMIC PRESS INC ELSEVIER SCIENCE 408 (1) 120 - 125 0006-291X 2011/04 [Refereed]
After partial hepatectomy (PH), regenerating liver accumulates unknown lipid species. Here, we analyzed lipids in murine liver and adipose tissues following PH by thin-layer chromatography (TLC), imaging mass spectrometry (IMS), and real-time RT-PCR. In liver, IMS revealed that a single TLC band comprised major 19 TG species. Similarly, IMS showed a single phospholipid TLC band to be major 13 species. In adipose tissues, PH induced changes to expression of genes regulating lipid metabolism. Finally, IMS of phosphatidylcholine species demonstrated distribution gradients in lobules that resembled hepatic zonation. IMS is thus a novel and power tool for analyzing lipid species with high resolution. (C) 2011 Elsevier Inc. All rights reserved. - Nobuhiro ZaimaNIPPON SUISAN GAKKAISHI JAPANESE SOC FISHERIES SCIENCE 77 (2) 260 - 260 0021-5392 2011/03
- Nobuhiro Zaima; Naoko Goto-Inoue; Kohsuke Adachi; Mitsutoshi SetouJOURNAL OF OLEO SCIENCE JAPAN OIL CHEMISTS SOC 60 (2) 93 - 98 1345-8957 2011/02 [Refereed]
Thin-layer chromatography (TLC) is an essential method for food composition analyses such as lipid nutrition analysis. TLC can be used to obtain information about the lipid composition of foods; however, it cannot be used for analyses at the molecular level. Recently we developed a new method that combines matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) with TLC-blotting (TLC-Blot-MALDI-IMS). The combination of MALDI-IMS and TLC blotting enabled detailed and sensitive analyses of lipids. In this study, we applied TLC-Blot-MALDI-IMS for analysis of major phospholipids extracted from bluefin tuna. We showed that TLC-Blot-MALDI-IMS analysis could visualize and identify major phospholipids such as phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, phosphatidylcholine, and sphingomyelin. - Kenji Onoue; Zaima Nobuhiro; Sugiura Yuki; Isojima Takuya; Okayama Satoshi; Horii Manabu; Akai Yasuhiro; Uemura Shiro; Takemura Genzou; Sakuraba Hitoshi; Sakaguchi Yasuhiro; Setou Mitsutoshi; Saito YoshihikoTHE JAPANESE CIRCULATION SOCIETY 1347-4820 2011/01
- Kenji Onoue; Nobuhiro Zaima; Yuki Sugiura; Takuya Isojima; Satoshi Okayama; Manabu Horii; Yasuhiro Akai; Shiro Uemura; Genzou Takemura; Hitoshi Sakuraba; Yasuhiro Sakaguchi; Mitsutoshi Setou; Yoshihiko SaitoCIRCULATION JOURNAL JAPANESE CIRCULATION SOC 75 (1) 221 - 223 1346-9843 2011/01
- Nobuhiro ZaimaNippon Suisan Gakkaishi (Japanese Edition) 77 (2) 260 0021-5392 2011
- 由木 大; 杉浦 悠毅; 財満 信宏; 瀬藤 光利実験医学 (株)羊土社 28 (20) 3228 - 3234 0288-5514 2010/12質量顕微鏡法は、質量分析を検出原理とした分子イメージング法である。組織や細胞中の生体分子の局在をノンプローブで直接的に検出し、さらに一度の測定で数百の分子を同時に可視化できるため、多様な分子種をもつ脂質の局在解析において非常に有効な手法である。現状では、脂肪酸組成の異なる脂質分子種を区別して可視化することが可能な唯一の方法である。本稿では、質量顕微鏡法による脂質イメージングの方法論とその具体例を紹介し、さらに医学的な応用への展望について概説したい。(著者抄録)
- Nobuhiro Zaima; Takahiro Hayasaka; Naoko Goto-Inoue; Mitsutoshi SetouINTERNATIONAL JOURNAL OF MOLECULAR SCIENCES MDPI AG 11 (12) 5041 - 5056 1422-0067 2010/12 [Refereed]
Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is a powerful tool that enables the simultaneous detection and identification of biomolecules in analytes. MALDI-imaging mass spectrometry (MALDI-IMS) is a two-dimensional MALDI-mass spectrometric technique used to visualize the spatial distribution of biomolecules without extraction, purification, separation, or labeling of biological samples. MALDI-IMS has revealed the characteristic distribution of several biomolecules, including proteins, peptides, amino acids, lipids, carbohydrates, and nucleotides, in various tissues. The versatility of MALDI-IMS has opened a new frontier in several fields such as medicine, agriculture, biology, pharmacology, and pathology. MALDI-IMS has a great potential for discovery of unknown biomarkers. In this review, we describe the methodology and applications of MALDI-IMS for biological samples. - Kamlesh Shrivas; Takahiro Hayasaka; Naoko Goto-Inoue; Yuki Sugiura; Nobuhiro Zaima; Mitsutoshi SetouANALYTICAL CHEMISTRY AMER CHEMICAL SOC 82 (21) 8800 - 8806 0003-2700 2010/11The ionic matrix (IM) is considered to be versatile for matrix-assisted laser desorption/ionization mass spectrometry (MAL)I-MS) for the identification of a wide range of biomolecules due to its good solubility for a variety of analytes, formation of homogeneous crystals with analytes, and high vacuum stability. When these advantages are exploited, the performance of IM of alpha-cyano-4-hydroxycinnamic acid butylamine (CHCAB) and 2,5-dihydroxybenzoic acid butylamine (DHBB) was compared with other matrixes for the identification of phospholipids in standard mixtures and mouse liver tissue sections. The results showed that the IM of CHCAB caused higher signal intensity and allowed the detection of a number phospholipids such as phosphatidylethanolamine (PE) and phosphatidylserine (PS) in addition to detection of phosphatidylcholine (PC) on the surface of the liver tissue sample. The IM of CHCAB was also used to identify the species of lipids present in different layers of cerebellum where the greater numbers of biomolecules were detected as compared to DHB matrix. Further, the feasibility of the proposed method was extended for the analysis of tryptic digested cytochrome c for increased signal intensity and number of peptide sequences in MALDI-MS. Thus, the application of IM to MALDI-MS could be a promising tool for imaging biomolecules in tissue sections in high throughput analyses with high sensitivity.
- H. Tanaka; N. Zaima; N. Yamamoto; D. Sagara; M. Suzuki; M. Nishiyama; Y. Mano; M. Sano; T. Hayasaka; N. Goto-Inoue; T. Sasaki; H. Konno; N. Unno; M. SetouEUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY W B SAUNDERS CO LTD 40 (5) 657 - 663 1078-5884 2010/11Background: The lipid metabolism of varicose veins (VVs) remains unknown. To elucidate the pathogenesis of VV, we utilized the novel technique of imaging mass spectrometry (IMS). Materials and methods: We obtained W tissues from 10 limbs of 10 W patients who underwent great saphenous vein stripping. As control vein samples, we harvested segmental vein tissues from 6 limbs of 6 patients with peripheral artery occlusive disease who underwent infra-inguinal bypass with reversed saphenous vein grafting. To identify the localisation of lipid molecules in the W tissues, we performed matrix-assisted laser desorption/ionization IMS (MALDI-IMS). We also performed MS/MS analyses to identify the structure of each molecule. Results: We obtained mass spectra directly from control vein tissues and VV tissues and found a unique localisation of lipid molecules in the VV tissues. We localised lysophosphatidylcholine (LPC) (1-acyl 16:0), phosphatidylcholine (PC) (1-acyl 36:4) and sphingomyelin (SM) (d18:1/16:0) at the site of the VV valve. Conclusion: MALDI-IMS revealed the distribution of various lipid molecules in normal veins and VVs both. Accumulation of LPC (1-acyl 16:0), PC (1-acyl 36:4) and SM (d18:1/16:0) in the VV tissues suggested that inflammation associated with abnormal lipid metabolism may contribute to the development of VV. (C) 2010 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.
- Naoko Goto-Inoue; Takahiro Hayasaka; Nobuhiro Zaima; Yukiyasu Kashiwagi; Mari Yamamoto; Masami Nakamoto; Mitsutoshi SetouJOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY SPRINGER 21 (11) 1940 - 1943 1044-0305 2010/11Glycosphingolipids (GSLs) are amphiphilic molecules consisting of a hydrophilic carbohydrate chain and a hydrophobic ceramide moiety. They appear to be involved primarily in biological processes such as cell proliferation, differentiation, and signaling. To investigate the mechanism of brain function in more detail, a more highly sensitive method that would reveal the GSL distribution in the brain is required. In this report, we describe a simple and efficient method for mapping the distribution and localization of GSLs present in mouse brain sections using nanoparticle-assisted laser desorption/ionization imaging mass spectrometry (IMS). We have developed and tested gold nanoparticles (AuNPs) as a new matrix to maximize the detection of GSLs. A matrix of AuNPs modified with alkylamine was used to detect various GSLs, such as minor molecular species of sulfatides and gangliosides, in mouse brain sections; these GSLs were hardly detected using 2,5-dihydroxybenzoic acid (DHB), which is the conventional matrix for GSLs. We achieved approximately 20 times more sensitive detection of GSLs using AuNPs compared to a DHB matrix. We believe that our new approach using AuNPs in IMS could lead to a new strategy for analyzing basic biological mechanisms and several diseases through the distribution of minor GSLs. (J Am Soc Mass Spectrom 2010, 21, 1940-1943) (C) 2010 American Society for Mass Spectrometry
- Hyun-Jeong Yang; Yuki Sugiura; Itsuko Ishizaki; Noriaki Sanada; Koji Ikegami; Nobuhiro Zaima; Kamlesh Shrivas; Mitsutoshi SetouSURFACE AND INTERFACE ANALYSIS JOHN WILEY & SONS LTD 42 (10-11) 1606 - 1611 0142-2421 2010/10Imaging mass spectrometry (IMS) provides a novel opportunity for visualization of molecular ion distribution. Currently, there are two major ionization techniques, matrix-assisted laser desorption/ionization (MALDI) and secondary ion mass spectrometry (SIMS) are widely used for imaging of biomolecules in tissue samples. MALDI and SIMS-based IMS have the following features; measurable mass ranges are wide and small, and the spatial resolutions are low and high, respectively. To the best of our knowledge, this is a first report to identify the lipids in cultured mammalian neurons by MALDI-IMS. Further, those neurons were analyzed with SIMS-IMS in order to compare the distribution pattern of lipids and other derived fragments. The parameters which influence the identification of lipids in cultured neurons were optimized in order to get an optimum detection of lipid molecules. The combined spatial data of MALDI and SIMS supported the idea that the signals of small molecules such as phosphatidylcholine head groups and fatty acids (detected in SIMS) are derived from the intact lipids (detected in MALDI-IMS). Copyright (C) 2010 John Wiley & Sons, Ltd.
- Morakot Sroyraya; Naoko Goto-Inoue; Nobuhiro Zaima; Takahiro Hayasaka; Piyachat Chansela; Supita Tanasawet; Kamlesh Shrivas; Prasert Sobhon; Mitsutoshi SetouSURFACE AND INTERFACE ANALYSIS JOHN WILEY & SONS LTD 42 (10-11) 1589 - 1592 0142-2421 2010/10 [Refereed]
We have developed an imaging mass spectrometer - the atmospheric-pressure mass microscope - with high spatial resolution, which is composed of an atmospheric pressure ion-source chamber for matrix-assisted laser desorption/ionization (AP-MALDI) and a quadrupole ion trap time-of-flight (QIT-TOF) mass spectrometer. The production of 2-dimensional mass spectrum intensity by the atmospheric-pressure mass microscope with a very fine scan pitch enables us to visualize the distribution of lipids and their metabolites in frozen sections without any specific probes or labels. In this study, we applied AP-MALDI-QIT-TOF imaging mass spectrometry to investigate the distribution of lipids in the compound eye-associated eyestalk of the blue swimming crab, Portunus pelagicus. The eyestalk of crustaceans responds to many signaling substances, and most of these substances are involved in lipid metabolism. The merged ion image of five significant biomolecules clearly showed seven separate zones in the eye and eyestalk. The results indicate that the lipid components of each cell layer of the compound eye are different. This study provides information regarding lipid compositions and locations on real tissue that correlate with function. Imaging mass spectrometry (IMS) with high spatial resolution could thus be a powerful tool for imaging and measurement of various samples for a first molecular screening. Copyright (C) 2010 John Wiley & Sons, Ltd. - Hyun-Jeong Yang; Itsuko Ishizaki; Noriaki Sanada; Nobuhiro Zaima; Yuki Sugiura; Ikuko Yao; Koji Ikegami; Mitsutoshi SetouMEDICAL MOLECULAR MORPHOLOGY SPRINGER TOKYO 43 (3) 158 - 164 1860-1480 2010/09Neurons have a large surface because of their long and thin neurites. This surface is composed of a lipid bilayer. Lipids have not been actively investigated so far because of some technical difficulties, although evidence from cell biology is emerging that lipids contain valuable information about their roles in the central nervous system. Recent progress in techniques, e.g., mass spectrometry, opens a new epoch of lipid research. We show herein the characteristic localization of phospholipid components in neurites by means of time-of-flight secondary ion mass spectrometry. We used explant cultures of mouse superior cervical ganglia, which are widely used by neurite investigation research. In a positive-ion detection mode, phospholipid head group molecules were predominantly detected. The ions of m/z 206.1 [phosphocholine, a common component of phosphatidylcholine (PC) and sphingomyelin (SM)] were evenly distributed throughout the neurites, whereas the ions of m/z 224.1, 246.1 (glycerophosphocholine, a part of PC, but not SM) showed relatively strong intensity on neurites adjacent to soma. In a negative-ion detection mode, fatty acids such as oleic and palmitic acids were mainly detected, showing high intensity on neurites adjacent to soma. Our results suggest that lipid components on the neuritic surface show characteristic distributions depending on neurite region.
- Nobuhiro Zaima; Naoko Goto-Inoue; Takahiro Hayasaka; Mitsutoshi SetouRAPID COMMUNICATIONS IN MASS SPECTROMETRY JOHN WILEY & SONS LTD 24 (18) 2723 - 2729 0951-4198 2010/09 [Refereed]
Rice is one of the most important food crops in the world and new varieties have been bred for specific purposes, such as the development of drought-resistance, or the enrichment of functional food factors. The localization and composition of metabolites in such new varieties must be investigated because all artificial interventions are expected to change the metabolites of rice. Imaging mass spectrometry using matrix-assisted laser desorption/ionization (MALDI-IMS) is a suitable tool for investigating the localization and composition of metabolites; however, suitable methodologies for the MALDI-IMS analysis of rice have not yet been established. In this study, we optimized the methods for analyzing rice grains by MALDI-IMS using adhesive film and found the characteristic distribution of metabolites in rice. Lysophosphatidylcholine (LPC) was localized in the endosperm. Phosphatidylcholine (PC), gamma-oryzanol and phytic acid were localized in the bran (germ and seed coat), and alpha-tocopherol was distributed in the germ (especially in the scutellum). In addition, MALDI-IMS revealed the LPC and PC composition of the rice samples. The LPC composition, LPC (1-acyl 16:0), LPC (1-acyl 18:2), LPC (1-acyl 18:1) and LPC (1-acyl 18:0), was 59.4 +/- 4.5%, 19.6 +/- 2.5%, 14.2 +/- 4.5% and 6.8 +/- 1.4%. The PC composition, PC (diacyl 16:0/18:2), PC (diacyl 16:0/18;1), PC (diacyl 18:1/18:3), PC (diacyl 18:1/18:2) and PC (diacyl 18:1/18:2), was 19.6 +/- 1.0%, 21.0 +/- 1.0%, 15.0 +/- 1.4%, 26.7 +/- 0.7% and 17.8 +/- 1.9%. This approach can be applied to the assessment of metabolites not only in rice, but also in other foods for which the preparation of sections is a challenging task. Copyright (c) 2010 John Wiley & Sons, Ltd. - Takahiro Hayasaka; Naoko Goto-Inoue; Nobuhiro Zaima; Kamlesh Shrivas; Yukiyasu Kashiwagi; Mari Yamamoto; Masami Nakamoto; Mitsutoshi SetouJOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY ELSEVIER SCIENCE INC 21 (8) 1446 - 1454 1044-0305 2010/08A new approach to the visualization of fatty acids in mouse liver and retinal samples has been developed using silver nanoparticles (AgNPs) in nanoparticle-assisted laser desorption/ionization imaging mass spectrometry (nano-PALDI-IMS) in negative ion mode. So far, IMS analysis has concentrated on main cell components, such as cell membrane phospholipids and cytoskeletal peptides. AgNPs modified with alkylcarboxylate and alkylamine were used for nano-PALDI-IMS to identify fatty acids, such as stearic, oleic, linoleic, arachidonic, and eicosapentaenoic acids, as well as palmitic acid, in mouse liver sections; these fatty acids are not detected using 2,5-dihydroxybenzoic acid (DHB) as a matrix. The limit of detection for the determination of palmitic acid was 50 pmol using nano-PALDI-IMS. The nano-PALDI-IMS method is successfully applied to the reconstruction of the ion images of fatty acids in mouse liver sections. We verified the detection of fatty acids in liver tissue sections of mice by analyzing standard lipid samples, which showed that fatty acids were from free fatty acids and dissociated fatty acids from lipids when irradiated with a laser. Additionally, we applied the proposed method to the identification of fatty acids in mouse retinal tissue sections, which enabled us to learn the six-zonal distribution of fatty acids in different layers of the retina. We believe that the current approach using AgNPs in nano-PALDI-IMS could lead to a new strategy to analyze basic biological mechanisms and several diseases through the distribution of fatty acids. (J Am Soc Mass Spectrom 2010, 21, 1446-1454) (C) 2010 American Society for Mass Spectrometry
- S. Kono; T. Nishio; Y. Takahashi; N. Goto-Inoue; M. Kinoshita; N. Zaima; H. Suzuki; A. Fukutoku-Otsuji; M. Setou; H. MiyajimaNEUROLOGY LIPPINCOTT WILLIAMS & WILKINS 75 (6) 547 - 554 0028-3878 2010/08Background: Filamin myopathy is associated with mutations in the filamin C gene ( FLNC) and is a myofibrillar myopathy characterized by focal myofibrillar destruction and cytoplasmic aggregates containing several Z-disk-related proteins. Methods: This study investigated 6 Japanese patients with dominantly inherited myofibrillar myopathy manifested by adult-onset, slow and progressive muscle weakness and atrophy in the distal extremities. Results: The abundantly expressed proteins in the affected muscles were identified as filamin C by nano liquid chromatography-tandem mass spectrometry. A genetic analysis of FLNC identified a heterozygous c.8107delG mutation that was localized to the dimerization domain of filamin C. A biochemical crosslinking analysis of bacterially expressed recombinant wild-type and mutant filamin C fragments demonstrated that the mutant monomer disturbed the proper dimerization of the wild-type filamin dimer, resulting in formation of a heterotrimer with the wild-type filamin dimer. The expression study in C2C12 myoblasts showed that the mutant filamin fragments formed cytoplasmic aggregates with endogenous wild-type filamin C. Conclusions: This study provides evidence for the dominant-negative effects of the FLNC mutation. These effects may be mutation-specific and likely result in the variation in the clinical phenotypes seen in patients with filamin myopathy. Neurology (R) 2010; 75: 547-554
- Naoko Goto-Inoue; Mitsutoshi Setou; Nobuhiro ZaimaANALYTICAL SCIENCES JAPAN SOC ANALYTICAL CHEMISTRY 26 (7) 821 - 825 0910-6340 2010/07 [Refereed]
We applied imaging mass spectrometry (IMS) to determine the spatial distribution of gamma-aminobutyric acid (GABA). We found that GABA had a specific localization in seeds. We also visualized various biomolecules as well as GABA with higher spatial resolution than in the previous report. Our work suggests that IMS might be a powerful tool for exploring functional food factors, investigating the specific distribution of nutrients in unused natural resources, and evaluating the quality of functional foods. - Sayaka Akieda-Asai; Nobuhiro Zaima; Koji Ikegami; Tomoaki Kahyo; Ikuko Yao; Takahiro Hatanaka; Shun-ichiro Iemura; Rika Sugiyama; Takeaki Yokozeki; Yoshinobu Eishi; Morio Koike; Kyoji Ikeda; Takuya Chiba; Haruyoshi Yamaza; Isao Shimokawa; Si-Young Song; Akira Matsuno; Akiko Mizutani; Motoji Sawabe; Moses V. Chao; Masashi Tanaka; Yasunori Kanaho; Tohru Natsume; Haruhiko Sugimura; Yukari Date; Michael W. McBurney; Leonard Guarente; Mitsutoshi SetouPLOS ONE PUBLIC LIBRARY SCIENCE 5 (7) 1932-6203 2010/07Background: SIRT1, a NAD-dependent deacetylase, has diverse roles in a variety of organs such as regulation of endocrine function and metabolism. However, it remains to be addressed how it regulates hormone release there. Methodology/Principal Findings: Here, we report that SIRT1 is abundantly expressed in pituitary thyrotropes and regulates thyroid hormone secretion. Manipulation of SIRT1 level revealed that SIRT1 positively regulated the exocytosis of TSH-containing granules. Using LC/MS-based interactomics, phosphatidylinositol-4-phosphate 5-kinase (PIP5K) c was identified as a SIRT1 binding partner and deacetylation substrate. SIRT1 deacetylated two specific lysine residues (K265/K268) in PIP5K gamma and enhanced PIP5K gamma enzyme activity. SIRT1-mediated TSH secretion was abolished by PIP5K gamma knockdown. SIRT1 knockdown decreased the levels of deacetylated PIP5K gamma, PI(4,5) P-2, and reduced the secretion of TSH from pituitary cells. These results were also observed in SIRT1-knockout mice. Conclusions/Significance: Our findings indicated that the control of TSH release by the SIRT1-PIP5K gamma pathway is important for regulating the metabolism of the whole body.
- 尾上 健児; 財満 信宏; 斎藤 能彦Endocrinology, diabetology & metabolism 科学評論社 30 (4) 359 - 367 1884-2917 2010/04
- Mitsutoshi Setou; Kamlesh Shrivas; Morakot Sroyraya; Hyunjeong Yang; Yuki Sugiura; Junji Moribe; Akira Kondo; Koji Tsutsumi; Yoshishige Kimura; Nobuya Kurabe; Takahiro Hayasaka; Naoko Goto-Inoue; Nobuhiro Zaima; Koji Ikegami; Prasert Sobhon; Yoshiyuki KonishiMEDICAL MOLECULAR MORPHOLOGY SPRINGER JAPAN KK 43 (1) 1 - 5 1860-1480 2010/03We have developed a mass microscopy technique, i.e., a microscope combined with high-resolution matrixassisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS), which is a powerful tool for investigating the spatial distribution of biomolecules without any time-consuming extraction, purification, and separation procedures for biological tissue sections. Mass microscopy provides clear images about the distribution of hundreds of biomolecules in a single measurement and also helps in understanding the cellular profile of the biological system. The sample preparation and the spatial resolution and speed of the technique are all important steps that affect the identification of biomolecules in mass microscopy. In this Award Lecture Review, we focus on some of the recent developments in clinical applications to show how mass microscopy can be employed to assess medical molecular morphology.
- 高山 達也; 財満 信宏; 宮崎 美紀; 高岡 直央; 京野 陽子; 伊藤 寿樹; 杉山 貴之; 永田 仁夫; 古瀬 洋; 栗田 豊; 麦谷 荘一; 瀬藤 光利; 大園 誠一郎日本泌尿器科学会雑誌 一般社団法人 日本泌尿器科学会 101 (2) 293 - 293 2010
- 榎元廣文; 井上菜穂子; 瀬藤光利; 財満信宏食品加工技術 日本食品機械研究会 30 (4) 153 - 159 1343-7836 2010 [Invited]
- Imaging mass spectrometry of gastric carcinoma in formalin-fixed paraffin-embedded tissue microarrayYoshifumi Morita; Koji Ikegami; Naoko Goto-Inoue; Takahiro Hayasaka; Nobuhiro Zaima; Hiroki Tanaka; Takashi Uehara; Tomohiko Setoguchi; Takanori Sakaguchi; Hisashi Igarashi; Haruhiko Sugimura; Mitsutoshi Setou; Hiroyuki KonnoCANCER SCIENCE WILEY-BLACKWELL PUBLISHING, INC 101 (1) 267 - 273 1347-9032 2010/01The popularity of imaging mass spectrometry (IMS) of tissue samples, which enables the direct scanning of tissue sections within a short time-period, has been considerably increasing in cancer proteomics. Most pathological specimens stored in medical institutes are formalin-fixed; thus, they had been regarded to be unsuitable for proteomic analyses, including IMS, until recently. Here, we report an easy-to-use screening method that enables the analysis of multiple samples in one experiment without extractions and purifications of proteins. We scanned, with an IMS technique, a tissue microarray (TMA) of formalin-fixed paraffin-embedded (FFPE) specimens. We detected a large amount of signals from trypsin-treated FFPE-TMA samples of gastric carcinoma tissues of different histological types. Of the signals detected, 54 were classified as signals specific to cancer with statistically significant differences between adenocarcinomas and normal tissues. We detected a total of 14 of the 54 signals as histological type-specific with the support of statistical analyses. Tandem MS revealed that a signal specific to poorly differentiated cancer tissue corresponded to histone H4. Finally, we verified the IMS-based finding by immunohistochemical analysis of more than 300 specimens spotted on TMAs; the immunoreactivity of histone H4 was remarkably strong in poorly differentiated cancer tissues. Thus, the application of IMS to FFPE-TMA can enable high-throughput analysis in cancer proteomics to aid in the understanding of molecular mechanisms underlying carcinogenesis, invasiveness, metastasis, and prognosis. Further, results obtained from the IMS of FFPE-TMA can be readily confirmed by commonly used immunohistochemical analyses. (Cancer Sci 2009).
- T. Harada; A. Yuba-Kubo; Y. Sugiura; N. Zaima; T. Hayasaka; N. Goto-Inoue; M. Wakui; M. Suematsu; K. Takeshita; K. Ogawa; Y. Yoshida; M. SetouAnal Chem 81 (21) 9153 - 7 1520-6882 2009/11We have developed a mass microscope (mass spectrometry imager with spatial resolution higher than the naked eye) equipped with an atmospheric pressure ion-source chamber for laser desorption/ionization (AP-LDI) and a quadrupole ion trap time-of-flight (QIT-TOF) analyzer. The optical microscope combined with the mass spectrometer permitted us to precisely determine the relevant tissue region prior to performing imaging mass spectrometry (IMS). An ultraviolet laser tightly focused with a triplet lens was used to achieve high spatial resolution. An atmospheric pressure ion-source chamber enables us to analyze fresh samples with minimal loss of intrinsic water or volatile compounds. Mass-microscopic AP-LDI imaging of freshly cut ginger rhizome sections revealed that 6-gingerol ([M + K](+)at m/z 333.15, positive mode; [M - H](-) at m/z 293.17, negative mode) and the monoterpene ([M + K](+) at m/z 191.09), which are the compounds related to pungency and flavor, respectively, were localized in oil drop-containing organelles. AP-LDI-tandem MS/MS analyses were applied to compare authentic signals from freshly cut ginger directly with the standard reagent. Thus, our atmosphere-imaging mass s
- Takahiro Harada; Akiko Yuba-Kubo; Yuki Sugiura; Nobuhiro Zaima; Takahiro Hayasaka; Naoko Goto-Inoue; Masatoshi Wakui; Makoto Suematsu; Kengo Takeshita; Kiyoshi Ogawa; Yoshikazu Yoshida; Mitsutoshi SetouANALYTICAL CHEMISTRY AMER CHEMICAL SOC 81 (21) 9153 - 9157 0003-2700 2009/11We have developed a mass microscope (mass spectrometry imager with spatial resolution higher than the naked eye) equipped with an atmospheric pressure ion-source chamber for laser desorption/ionization (AP-LDI) and a quadrupole ion trap time-of-flight (QIT-TOF) analyzer. The optical microscope combined with the mass spectrometer permitted us to precisely determine the relevant tissue region prior to performing imaging mass spectrometry (IMS). An ultraviolet laser tightly focused with a triplet lens was used to achieve high spatial resolution. An atmospheric pressure ion-source chamber enables us to analyze fresh samples with minimal loss of intrinsic water or volatile compounds. Mass-microscopic AP-LDI imaging of freshly cut ginger rhizome sections revealed that 6-gingerol ([M + K](+) at m/z 333.15, positive mode; [M - H](-) at m/z 293.17, negative mode) and the monoterpene ([M + Kr](-) at m/z 191.09), which are the compounds related to pungency and flavor, respectively, were localized in oil drop-containing organelles. AP-LDI-tandem MS/MS analyses were applied to compare authentic signals from freshly cut ginger directly with the standard reagent. Thus, our atmosphere-imaging mass spectrometer enabled us to monitor a quality of plants at the organelle level.
- T. Takayama; N. Zaima; Y. Kyono; M. Miyazaki; N. Takaoka; M. Nagata; F. Kai; T. Sugiyama; M. Setou; S. OzonoEJC SUPPLEMENTS PERGAMON-ELSEVIER SCIENCE LTD 7 (2) 435 - 435 1359-6349 2009/09
- Naoko Goto-Inoue; Takahiro Hayasaka; Nobuhiro Zaima; Mitsutoshi SetouGLYCOBIOLOGY OXFORD UNIV PRESS INC 19 (9) 950 - 957 0959-6658 2009/09More than 90% of the glycolipid in mammalian testis consists of a unique sulfated glyceroglycolipid called seminolipid. The galactosylation of the molecule is catalyzed by UDP-galactose:ceramide galactosyltransferase (CGT). Disruption of the CGT gene in mice results in male infertility due to the arrest of spermatogenesis, indicating that seminolipid plays an important role in reproductive function. Seminolipid molecules can be assigned to different molecular species based on the fatty acid composition. In this report, we investigated the localizations of the molecular species of seminolipid by imaging mass spectrometry and demonstrated that major molecule (C16:0-alkyl-C16:0-acyl) was expressed throughout the tubules: some (C16:0-alkyl-C14:0-acyl and C14:0-alkyl-C16:0-acyl) were predominantly expressed in spermatocytes and the other (C17:0-alkyl-C16:0-acyl) was specifically expressed in spermatids and spermatozoa. This is the first report to show the cell-specific localization of each molecular species of seminolipid during testicular maturation.
- Takahiro Hayasaka; Naoko Goto-Inoue; Nobuhiro Zaima; Yoshishige Kimura; Mitsutoshi SetouLIPIDS SPRINGER HEIDELBERG 44 (9) 837 - 848 0024-4201 2009/09Imaging mass spectrometry (IMS) has been developed as a method for determining and visualizing the distribution of proteins and lipids across sections of dissected tissue. Although lipids play an important role in mammal development, their detailed distributions have not been analyzed by conventional methods. In this study, we tried to determine and visualize lysophosphatidylcholine (LysoPtdCho) and triacylglycerol (TAG) in a mouse embryo by matrix-assisted laser desorption/ionization (MALDI) hybrid quadrupole time-of-flight (TOF) mass spectrometer. Many peaks were detected from a raster scan of the whole embryonic sections. The peaks at m/z 496.33, 524.36, 879.72, 881.74, and 921.74 were identified by MS/MS analyses as [LysoPtdCho (16:0) + H](+), [LysoPtdCho (18:0) + H](+), [TAG (16:0/18:2/18:1) + Na](+), [TAG (16:0/18:1/18:1) + Na](+), and [TAG (16:0/20:3/18:1) + K](+), respectively. The ion images constructed from the peaks revealed that LysoPtdCho were distributed throughout the body and TAGs were distributed around the brown adipose tissue and in the liver at embryo day 17.5. Thus, IMS system based on MALDI hybrid quadrupole TOF MS revealed the distribution of LysoPtdCho and, more importantly, the organ-specific distribution of TAGs in the embryonic stages of mammals for the first time. We can conclude that this technique enables us to analyze the roles of various lipids during embryogenesis and gives insight for lipid research.
- Yuki Sugiura; Yoshiyuki Konishi; Nobuhiro Zaima; Shigeki Kajihara; Hiroki Nakanishi; Ryo Taguchi; Mitsutoshi SetouJOURNAL OF LIPID RESEARCH AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC 50 (9) 1776 - 1788 0022-2275 2009/09Previous studies have shown that MALDI-imaging mass spectrometry (IMS) can be used to visualize the distribution of various biomolecules, especially lipids, in the cells and tissues. In this study, we report the cell-selective distribution of PUFA-containing glycerophospholipids (GPLs) in the mouse brain. We established a practical experimental procedure for the IMS of GPLs. We demonstrated that optimization of the composition of the matrix solution and spectrum normalization to the total ion current (TIC) is critical. Using our procedure, we simultaneously differentiated and visualized the localizations of specific molecular species of GPLs in mouse brain sections. The results showed that PUFA-containing phosphatidylcholines (PCs) were distributed in a cell-selective manner: arachidonic acid-and docosahexaenoic acid-containing PCs were seen in the hippocampal neurons and cerebellar Purkinje cells, respectively. Furthermore, these characteristic localizations of PUFA-PCs were formed during neuronal maturation. The phenomenon of brain cell-selective production of specific PUFA-GPLs will help elucidate the potential physiological functions of PUFAs in specific brain regions.-Sugiura, Y., Y. Konishi, N. Zaima, S. Kajihara, H. Nakanishi, R. Taguchi, and M. Setou. Visualization of the cell-selective distribution of PUFA-containing phosphatidylcholines in mouse brain by imaging mass spectrometry. J. Lipid Res. 2009. 50: 1776-1788.
- Nobuhiro Zaima; Takahiro Hayasaka; Naoko Goto-Inoue; Mitsutoshi SetouJOURNAL OF OLEO SCIENCE JAPAN OIL CHEMISTS SOC 58 (8) 415 - 419 1345-8957 2009/08 [Refereed]
Visualization of endogenous molecules in small experimental animals is very important in order to investigate the localization of specific molecules. Conventional imaging techniques are not suitable for simultaneous visualization of endogenous molecules. We recently developed a new imaging method-imaging mass spectrometry (IMS) using matrix-assisted laser desorption/ionization quadrupole ion trap time-of-flight (MALDI-QIT-TOF). In this study, we applied IMS using MALDI-QIT-TOF to visualize the metabolites in medaka (Oryzias latipes) sections and determined the spatial distribution of metabolites including lipids. - Nobuhiro Zaima; Yumiko Matsuyama; Mitsutoshi SetouJOURNAL OF OLEO SCIENCE JAPAN OIL CHEMISTS SOC 58 (5) 267 - 273 1345-8957 2009/05 [Refereed]
Non-alcoholic steatohepatitis (NASH) is a common liver disease. NASH is characterized by fatty liver, along with inflammation. Most people with NASH are not aware of their condition, even though NASH can lead to hepatic cirrhosis. Several approaches have been tested to clarify the pathology of NASH. However, the mechanism of onset of NASH was not well-defined. In this study, a supervised multivariate analysis (principal component analysis) approach using direct matrix-assisted laser desorption/ionization mass spectrometry (dMALDI-MS) was applied to the analysis of metabolites in starvation-induced fatty liver tissue sections. This approach does not require complex pretreatments. We investigated the characteristic dynamics of metabolites in fatty liver. This approach can be applied to the analysis of human biopsy specimens of fatty liver in future studies. - Hiroshi Ageta; Sayaka Asai; Yuki Sugiura; Naoko Goto-Inoue; Nobuhiro Zaima; Mitsutoshi SetouMEDICAL MOLECULAR MORPHOLOGY SPRINGER TOKYO 42 (1) 16 - 23 1860-1480 2009/03Lipids are major structural component of the brain and play key roles in signaling functions in the central nervous system (CNS), such as the hippocampus. In particular, sulfatide is an abundant glycosphingolipid component of both the central and the peripheral nervous system and is an essential lipid component of myelin membranes. Lack of sulfatide is observed in myelin deformation and neurological deficits. Previous studies with antisulfatide antibody have investigated distribution of sulfatide expression in neurons; however, this method cannot distinguish the differences of sulfatide lipid species raised by difference of carbon-chain length in the ceramide portion in addition to the differences of sulfatide and seminolipid. In this study, we solved the problem by our recently developed nanoparticle-assisted laser desorption/ionization (nano-PALDI)-based imaging mass spectrometry (IMS). We revealed that the level of sulfatide in the middle molecular layer was significantly higher than that in granule cell layers and the inner molecular layer in the dentate gyrus of rat hippocampus.
- Ken-ichi Hirano; Yoshihiko Ikeda; Nobuhiro Zaima; Yasuhiko Sakata; Goro MatsumiyaNEW ENGLAND JOURNAL OF MEDICINE MASSACHUSETTS MEDICAL SOC 359 (22) 2396 - 2398 0028-4793 2008/11 [Refereed]
- Takahiro Hayasaka; Naoko Goto-Inoue; Yuki Sugiura; Nobuhiro Zaima; Hiroki Nakanish; Kentaro Ohishi; Setsuko Nakanish; Takayuki Naito; Ryo Taguchi; Mitsutoshi SetouRAPID COMMUNICATIONS IN MASS SPECTROMETRY JOHN WILEY & SONS LTD 22 (21) 3415 - 3426 0951-4198 2008/11 [Refereed]
We recently developed a matrix-assisted laser desorption/ionization quadrupole ion trap time-of-flight (MALDI-QIT-TOF)-based imaging mass spectrometry (IMS) system. This system enables us to perform structural analyses using tandem mass spectrometry (MS/MS), as well as to visualize phospholipids and peptides in frozen sections. In the retina, phototransduction is regulated by the light-sensitive interaction between visual pigment-coupled receptor proteins, such as rhodopsin, and G proteins, such as transducin. There are some reports that the conformation of rhodopsin is influenced by the composition of phospholipids in the lipid bilayer membrane. However, these results were based on in vitro experiments and have not been analyzed in vivo. In this study, we visualized and identified phospholipids in mouse retinal sections with the MALDI-QIT-TOF-based IMS system. From a spectrum obtained by raster-scanned analysis of the sections, ions with high signal intensities were selected and analyzed by MS/MS. As a result, sixteen ions were identified as being from four diacyl-phosphatidylcholine (PC) species, i.e., PC (16:0/16:0), PC (16:0/18:1), PC (16:0/22:6), and PC (18:0/22:6), with different ion forms. The ion images revealed different distributions on the retinal sections: PC (16:0/18:1) was distributed in the inner nuclear layer and outer plexiform layer, PC (16:0/16:0) in the outer nuclear layer and inner segment, and both PC (16:0/22:6) and PC (18:0/22:6) in the outer segment and pigment epithelium. In conclusion, our in vivo IMS analyses demonstrated a three-zone distribution of PC species on the retinal sections. This approach may be useful for analyzing lipid changes and their contribution to phototransduction in the retina. Copyright (C) 2008 John Wiley & Sons, Ltd. - T. Okada; R. Noguchi; M. Hosokawa; K. Fukunaga; T. Nishiyama; N. Zaima; T. Hirata; K. MiyashitaJOURNAL OF FOOD SCIENCE BLACKWELL PUBLISHING 73 (8) H201 - H206 0022-1147 2008/10Trans and conjugated fatty acids may exhibit either beneficial or detrimental bioactive effects depending on their metabolic properties. This study was conducted to elucidate if isomerization and conjugation of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) demonstrate more favorable bioactivity on lipid metabolism compared to unmodified EPA and DHA. The effects of dietary intake of trans and conjugated forms of EPA and DHA on lipid metabolism were evaluated in animal trials and compared to a control group fed soybean oil. None of the experimental diets showed significant differences from the control in terms of body weight; however, the white adipose tissue weight of rodents fed trans DHA, conjugated EPA (CEPA), and conjugated DHA (CDHA) was significantly lower than the control. Triacylglycerol levels in plasma were significantly decreased in groups fed trans DHA (17.2 mg/dL) and CDHA (31.9 mg/dL) relative to the control (51.3 mg/dL). The total cholesterol concentrations were significantly lower than the control (68.0 mg/dL) in all experimental groups (47.3 to 53.7 mg/dL) except CEPA (58.3 mg/dL). Fatty acid compositions of lipids extracted from rodent livers were influenced by the dietary fatty acid profiles, with all groups showing higher concentrations of stearic acid and lower levels of linoleic acid compared to the control. Rodents fed trans DHA did not have detectable levels of these fatty acid isomers in their livers, suggesting either quick metabolism or a difficulty with bio-absorption.
- Shuichi Shimma; Yuki Sugiura; Takahiro Hayasaka; Nobuhiro Zaima; Mineo Matsumoto; Mitsutoshi SetouANALYTICAL CHEMISTRY AMER CHEMICAL SOC 80 (3) 878 - 885 0003-2700 2008/02 [Refereed]
Imaging mass spectrometry is becoming a popular visualization technique in the medical and biological sciences. For its continued development, the ability to both visualize and identify molecules directly on the tissue surface using tandem mass spectrometry (MSn) is essential. We established an imaging system based on a matrix-assisted laser/desorption ionization quadrupole ion trap time-of-flight type instrument (AXIMA-QIT, Shimadzu, Kyoto, Japan), which was compatible with both imaging and highly sensitive MSn. In this paper, we present the operating conditions of the AXIMA-QIT as an imaging instrument and introduce the data converter we developed that is available free of charge. The converted data can be applied to Biomap, the commonly used visualization software. For the feasibility experiments, we demonstrated the visualization of phospholipids, glycolipid, and tryptic-digested proteins in the mouse cerebellum. The visualized lipids were successfully identified by MSn directly on the tissue surface, with a strong ability to isolate precursor ions. In the analysis of tryptic-digested proteins, we compared the product ion spectra between AXIMA-QIT and a tandem TOF-type instrument. The results confirmed that AXIMA-QIT can provide a high quality of product ion spectra even on the tissue surface. - Nobuhiro Zaima; Tatsuya Sugawara; Yuki Otsubo; Takashi HirataFISHERIES SCIENCE BLACKWELL PUBLISHING 73 (4) 897 - 901 0919-9268 2007/08 [Refereed]
Trans geometric isomers of eicosapentaenoic acid (TEPA) have been found as minor components in human platelets. However, there is little information on the mechanism of trans-isomerization of eicosapentaenoic acid (EPA) in vitro and in vivo. The effects of reactive radicals and heat on trans-isomerization of EPA were examined. Trans-isomerization occurred when EPA ethyl ester reacted with nitrogen dioxide radical (NO2) but not with 2,2'-azobis(2,4-dimethylvaleronitrile). TEPA was also produced from EPA ethyl ester heated at 200 degrees C for 60 h. No TEPA, however, was detected in sardines Sardinops melanostictus after boiling, roasting, or microwave heating. These results suggest that EPA is trans-isomerized by NO2 in vivo while trans-isomerization of EPA does not occur during conventional cooking. - Tatsuya Sugawara; Nobuhiro Zaima; Akiyo Yamamoto; Shota Sakai; Ryoko Noguchi; Takashi HirataBIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY TAYLOR & FRANCIS LTD 70 (12) 2906 - 2912 0916-8451 2006/12 [Refereed]
Sea cucumber is a health-beneficial food, and contains a variety of physiologically active substances including glycosphingolipids. We show here the sphingoid base composition of cerebrosides prepared from sea cucumber and the cytotoxicity against human colon cancer cell lines. The composition of sphingoid bases prepared from sea cucumber was different from that of mammals, and the major constituents estimated from mass spectra had a branched C17-19 alkyl chain with 1-3 double bonds. The viability of DLD-1, WiDr and Caco-2 cells treated with sea cucumber sphingoid bases was reduced in a dose-dependent manner and was similar to that of cells treated with sphingosine. The sphingoid bases induced such a morphological change as condensed chromatin fragments and increased the caspase-3 activity, indicating that the sphingoid bases reduced the cell viability by causing apoptosis in these cells. Sphingolipids of sea cucumber might therefore serve as bioactive dietary components to suppress colon cancer. - Nobuhiro Zaima; Tatsuya Sugawara; Dai Goto; Takashi HirataJOURNAL OF LIPID RESEARCH AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC 47 (12) 2712 - 2717 0022-2275 2006/12 [Refereed]
Dietary mono-or di-trans fatty acids with chain lengths of 18-22 increase the risk of cardiovascular diseases because they increase LDL cholesterol and decrease HDL cholesterol in the plasma. However, the effects of trans isomers of PUFAs on lipid metabolism remain unknown. Dietary PUFAs, especially eicosapentaenoic acid (EPA) in marine oils, improve serum lipid profiles by suppressing liver X receptor alpha (LXR alpha) activity in the liver. In this study, we compared the effects of trans geometric isomers of eicosapentaenoic acid ( TEPA) on triacylglycerol synthesis induced by a synthetic LXR alpha agonist ( T0901317) with the effects of EPA in HepG2 cells. TEPA significantly decreased the amount of cellular triacylglycerol and the expression of mRNAs encoding fatty acid synthase, stearoyl-CoA desaturase-1, and glycerol-3-phosphate acyltransferase induced by T0901317 compared with EPA. However, there was no significant difference between the suppressive effect of TEPA or EPA on the expression of sterol-regulatory element binding protein-1c (SREBP-1c) induced by T0901317. We found that TEPA, but not EPA, decreased the mRNA expression of peroxisome proliferator-activated receptor gamma coactivator 1 beta(PGC-1 beta), which is a coactivator of both LXR alpha and SREBP-1. These results suggest that the hypolipidemic effect of TEPA can be attributed to a decrease not only in SREBP-1 but also in PGC-1b expression. - Daisuke Tatsumi; Nobuhiro Zaima; Takayoshi Matsumoto; Hidehiko Sugiyama; Haruo TakahashiZairyo/Journal of the Society of Materials Science, Japan 55 (4) 363 - 366 0514-5163 2006/04Kenaf is a fast-growing plant and is noticed as a nonwood fiber resource. There will be significance in the kenaf utilization when the unique characteristics of kenaf will be effective for certain purposes. In this study, pulping and bleaching of kenaf were carried out to examine the usability of kenaf as a fibrous material. We examined a hydrotropic pulping and an enzymatic bleaching, considering the environmental feasibility. Sodium m-xylene sulfonate solution (NaXS) and sodium p-toluene sulfonate solution (NaTS) were used as the hydrotropic regents. The characteristic peaks for lignin were detected by means of UV, 13C-NMR, and FT-IR measurements of the solution after the hydrotropic cooking. The solution after the NaTS cooking produced precipitation when it was stand at room temperature, although the NaXS was stable. This shows that NaXS has higher power of dissolution of lignin. The molecular orbital calculation implied that this difference was originated from the micelle forming ability of the regents. The enzymatic bleaching by manganese peroxidase (MnP) was applied for the obtained pulp. The brightness was increased in 17.4% and the Kappa number was lowered in 9.0 for the bast fibers by the biobleaching.
- Daisuke Tatsumi; Nobuhiro Zaima; Takayoshi Matsumoto; Hidehiko Sugiyama; Haruo TakahashiZairyo/Journal of the Society of Materials Science, Japan 社団法人日本材料学会 55 (4) 363 - 366 0514-5163 2006/04Kenaf is a fast-growing plant and is noticed as a nonwood fiber resource. There will be significance in the kenaf utilization when the unique characteristics of kenaf will be effective for certain purposes. In this study, pulping and bleaching of kenaf were carried out to examine the usability of kenaf as a fibrous material. We examined a hydrotropic pulping and an enzymatic bleaching, considering the environmental feasibility. Sodium m-xylene sulfonate solution (NaXS) and sodium p-toluene sulfonate solution (NaTS) were used as the hydrotropic regents. The characteristic peaks for lignin were detected by means of UV, 13C-NMR, and FT-IR measurements of the solution after the hydrotropic cooking. The solution after the NaTS cooking produced precipitation when it was stand at room temperature, although the NaXS was stable. This shows that NaXS has higher power of dissolution of lignin. The molecular orbital calculation implied that this difference was originated from the micelle forming ability of the regents. The enzymatic bleaching by manganese peroxidase (MnP) was applied for the obtained pulp. The brightness was increased in 17.4% and the Kappa number was lowered in 9.0 for the bast fibers by the biobleaching.
- Nobuhiro Zaima; Tatsuya Sugawara; Hirofumi Arai; Kazuyuki Nakamura; Mikako Takasugi; Kenji Fukunaga; Ryoko Noguchi; Takashi HirataJournal of Oleo Science 54 (9) 505 - 512 1347-3352 2005 [Refereed]
Although trans geometric isomers of unsaturated fatty acids are formed during heat treatment, little is known about the physicochemical properties and the bioactivities of trans eicosapentaenoic acid (TEPA). We examined the oxidative stability and the anti-inflammatory activity of TEPA prepared using p-toluenesulfinic acid. TEPA was more stable to oxidation induced by radical generators than eicosapentaenoic acid (EPA) in organic and in aqueous solutions, and was less suitable as a substrate for 15-lipoxygenase oxidation than was EPA. These results suggest that the trans conformation may be a more stable structure to oxidation. In addition, the release of leukotriene B4 (LTB4) from Ca-ionophore-stimulated rat peritoneal exudate cells (PEC) was not affected by treatment with TEPA, and TEPA was taken up into PEC at lower levels compared to EPA. These results suggest that dietary TEPA has different physiological effects than EPA. © 2005, Japan Oil Chemists' Society. All rights reserved.
MISC
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- 久後 裕菜; 藤嶋 玲奈; 森山 達哉; 財満 信宏 日本病態生理学会雑誌 28- (2) 56 -56 2019/07
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- Tabebuia avellanedaeから単離された脂肪蓄積予防活性を有するイリドイドの合成山下 光明; 畑 柊平; 早川 眞矢; 村上 穂乃佳; 福田 陽一; 家田 彩菜; 岩本 和子; 財満 信宏; 森山 達哉; 飯田 彰 2019/03
- 家田彩菜; 高田祐一; 岩本和子; 財満信宏; 財満信宏; 森山達哉; 森山達哉 アグリバイオ 3- (1) 47‐51 2019/01
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- 久後裕菜; 財満信宏; 財満信宏; 田中宏樹; 柳本賢一; 佐々木健; 浦野哲盟; 海野直樹; 海野直樹; 森山達哉; 森山達哉 脈管学(Web) 58- (supplement) 2018
- 財満信宏; 財満信宏; 久後裕菜; 田中宏樹; 佐々木健; 浦野哲盟; 海野直樹; 海野直樹; 森山達哉; 森山達哉 脈管学(Web) 58- (supplement) 2018
- 家田彩菜; 高田祐一; 奥野悠子; 岩本和子; 財満信宏; 財満信宏; 財満信宏; 森山達哉; 森山達哉; 森山達哉 日本栄養・食糧学会近畿支部大会および公開シンポジウム講演抄録集 57th- 2018
- 家田彩菜; 高田祐一; 奥野悠子; 岩本和子; 財満信宏; 財満信宏; 財満信宏; 森山達哉; 森山達哉; 森山達哉 日本食品科学工学会関西支部大会市民フォーラム講演要旨集 1st- 2018
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- 村上 浩規; 財満 信宏; 森山 達哉 栄養 2- (4) 203 -213 2017/12
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- 小川昂志; 高葢秋穂; 村上浩規; 岩本和子; 矢野えりか; 財満信宏; 森山達哉 日本栄養・食糧学会近畿支部大会および公開シンポジウム講演抄録集 56th- 50 2017/11
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- 植田啄也; 矢野えりか; 立垣愛郎; 財満信宏; 森山達哉 日本栄養・食糧学会近畿支部大会および公開シンポジウム講演抄録集 56th- 29 2017/11
- 徳舛直樹; 花房佳世; 野地和音; 矢野えりか; 財満信宏; 森山達哉 月刊アレルギーの臨床 (503) 856‐859 2017/08
- 腹部大動脈瘤の破裂機構の解明と破裂予防法の検討財満 信宏; 久後 裕菜; 田中 宏樹; 柳本 賢一; 佐々木 健; 浦野 哲盟; 海野 直樹; 森山 達哉 脂質生化学研究 59- 43 -43 2017/06
- 腹部大動脈瘤の破裂機構の解明と破裂予防法の検討財満 信宏; 久後 裕菜; 田中 宏樹; 柳本 賢一; 佐々木 健; 浦野 哲盟; 海野 直樹; 森山 達哉 脂質生化学研究 59- 43 -43 2017/06
- 血管壁に異常出現した脂肪細胞が腹部大動脈瘤破裂を誘導する久後 裕菜; 財満 信宏; 田中 宏樹; 毛利 陽平; 柳本 賢一; 佐々木 健; 浦野 哲盟; 海野 直樹; 森山 達哉 日本栄養・食糧学会大会講演要旨集 71回- 340 -340 2017/04
- 村上浩規; 植田啄也; 矢野えりか; 岩本和子; 財満信宏; 森山達哉 月刊アレルギーの臨床 37- (497) 265‐268 -268 2017/03
- 植田啄也; 花房佳世; 矢野えりか; 岩本和子; 財満信宏; 森山達哉 月刊アレルギーの臨床 37- (495) 58‐61 -61 2017/01
- 「アレルギー疾患の発症・増悪の予防-最新のアプローチ-」に寄せる 競合ELISA法による大豆アレルゲンGly m4の定量の試み花房 佳世; 植田 啄也; 矢野 えりか; 財満 信宏; 森山 達哉 アレルギーの臨床 36- (9) 874 -878 2016/08
- 久後 裕菜; 山本 彩実; 森山 達哉; 財満 信宏 オレオサイエンス 16- (5) 225 -231 2016/05
- ヒト腹部大動脈瘤の病理解析と新規モデル動物の作出財満 信宏; 久後 裕菜; 田中 宏樹; 海野 直樹; 森山 達哉 日本栄養・食糧学会大会講演要旨集 70回- 295 -295 2016/04
- 腹部大動脈瘤発症に対する魚油の予防効果の検討久後 裕菜; 財満 信宏; 毛利 陽平; 田中 宏樹; 柳本 賢一; 浦野 哲盟; 海野 直樹; 森山 達哉 日本栄養・食糧学会大会講演要旨集 70回- 296 -296 2016/04
- KUGO Hirona; YAMAMOTO Ayami; MORIYAMA Tatsuya; ZAIMA Nobuhiro Journal of the Mass Spectrometry Society of Japan 64- (1) 11 -15 2016
- 新しい腹部大動脈瘤動物モデルの開発 大動脈壁の虚血が瘤化を惹起する田中 宏樹; 財満 信宏; 佐々木 健; 山本 尚人; 犬塚 和徳; 佐野 真規; 斎藤 貴明; 杉澤 良太; 片橋 一人; 矢田 達朗; 今野 弘之; 浦野 哲盟; 瀬藤 光利; 海野 直樹 脈管学 55- (Suppl.) S122 -S122 2015/10
- Variability analysis of pan-allergen (PR-5,PR-10, profilin) levels of plant-foods infected by fungi.MORIYAMA Tatsuya アレルギーの臨床 35- (9) 876 -879 2015/09 [Refereed][Invited]
- アントシアニンの体内動態解析財満 信宏; 稲葉 栞里; 藤森 隆道; 荘厳 哲哉; 小林 沙織; 森山 達哉 JSBMS Letters 40- (Suppl.) 98 -98 2015/08
- アントシアニンの体内動態解析財満 信宏; 稲葉 栞里; 藤森 隆道; 荘厳 哲哉; 小林 沙織; 森山 達哉 JSBMS Letters 40- (Suppl.) 98 -98 2015/08
- 田中 宏樹; 財満 信宏; 佐々木 健; 今野 弘之; 瀬藤 光利; 海野 直樹 静脈学 26- (3) 227 -235 2015/08
- ZAIMA NOBUHIRO; KOORI TOSHIYUKI; MORIYAMA TATSUYA; KAWANISHI TAKAHIKO; TERASHITA TAKAO; SHIRASAKA NORIFUMI 日本農芸化学会大会講演要旨集(Web) 2015- 4F26P08 (WEB ONLY) 2015/03
- 田中宏樹; 田中宏樹; 財満信宏; 佐々木健; 山本尚人; 犬塚和徳; 佐野真規; 斎藤貴明; 杉澤良太; 片橋一人; 矢田達朗; 今野弘之; 浦野哲盟; 瀬藤光利; 海野直樹 脈管学(Web) 55- (supplement) 2015
- Variability analysis of resistin involved in inflammation and allergyMORIYAMA Tatsuya The Allergy in Practice 35- (14) 58 -61 2015 [Refereed]
- F. Ijaz; K. Tsutsumi; Y. Hatanaka; T. Hatanaka; S. Asai-Akeida; N. Zaima; K. Ikegami; M. Setou MOLECULAR BIOLOGY OF THE CELL 25- 2014/12
- 上田和典; 上田和典; 笠井彩加; 土岐倉千智; 福田陽一; 福田陽一; 山下光明; 財満信宏; 森山達哉; 飯田彰 機能性食品と薬理栄養 8- (5) 461 2014/12
- ドコサヘキサエン酸は腎がんの進展を抑制する(Docosahexaenoic acid inhibits the progression of renal cancer)高山 達也; 高岡 直久; 財満 信宏; 潭 成; 宮崎 美紀; 杉山 貴之; 森田 辰男; 瀬藤 光利; おおぞの せいいちろう 日本癌学会総会記事 73回- P -3212 2014/09
- 飯田彰; 上田和典; 大川貴弘; 岩竹さゆり; 山本美里; 福田陽一; 山下光明; 財満信宏; 森山達哉 日本補完代替医療学会学術集会プログラム・抄録集 17th- 86 2014
- 上田和典; 笠井彩加; 土岐倉千智; 福田陽一; 山下光明; 財満信宏; 森山達哉; 飯田彰 日本補完代替医療学会学術集会プログラム・抄録集 17th- 88 2014
- 庄野 陽祐; 小谷口 美也子; 藤原 美乃里; 中屋 慎; 財満 信宏; 北村 進一 応用糖質科学 : 日本応用糖質科学会誌 3- (3) B34 2013/08
- T. Takayama; N. Zaima; N. Takaoka; M. Miyazaki; C. Tan; T. Sugiyama; H. Furuse; S. Mugiya; M. Setou; S. Ozono UROLOGY 80- (3) S247 -S248 2012/09
- 動脈硬化の臨床と病理 腹部大動脈瘤壁外膜vaso vasorumの動脈硬化と瘤壁組織の低酸素についての病理学的研究海野 直樹; 田中 宏樹; 財満 信宏; 佐々木 健; 山本 尚人; 鈴木 実; 眞野 勇記; 佐野 真規; 斉藤 貴明; 杉澤 良太; 今野 弘之; 瀬藤 光利 脈管学 52- (Suppl.) S78 -S79 2012/09
- N. Goto-Inoue; T. Hayasaka; N. Zaima; K. Nakajima; W. M. Holleran; S. Sano; M. Setou; Y. Uchida JOURNAL OF INVESTIGATIVE DERMATOLOGY 132- S54 -S54 2012/05
- 海野直樹; 田中宏樹; 田中宏樹; 財満信宏; 財満信宏; 佐々木健; 山本尚人; 鈴木実; 眞野勇記; 佐野真規; 斉藤貴明; 杉澤良太; 今野弘之; 瀬藤光利 脈管学(Web) 52- (supplement) 2012
- 武田健吾; 植田浩一; 財満信宏; 森山達哉; 河村幸雄; 畑中顯和; 松田一彦 日本農芸化学会大会講演要旨集(Web) 2012- 2012
- リンパ還流不全による静脈壁並びに静脈周囲組織変性についての実験的検討田中 宏樹; 海野 直樹; 山本 尚人; 鈴木 実; 眞野 勇記; 佐野 真規; 斉藤 貴明; 財満 信宏; 佐々木 健; 今野 弘之; 瀬藤 光利 脈管学 51- (Suppl.) S100 -S100 2011/09
- 循環器疾患の制圧に向けて 心血管病理病態研究の新展開 腹部大動脈瘤と外膜の脂肪細胞化瀬藤 光利; 田中 宏樹; 財満 信宏; 海野 直樹; 今野 弘之 日本病理学会会誌 100- (1) 223 -223 2011/03
- 矢尾育子; 矢尾育子; 杉浦悠毅; 杉浦悠毅; 財満信宏; 瀬藤光利; 伊藤誠二 JSBMS Letters 36- (Supplement) 2011
- S. Kono; T. Nishio; Y. Takahashi; N. Goto-Inoue; M. Kinoshita; N. Zaima; H. Suzuki; A. Fukutoku-Otsuji; M. Setou; H. Miyajima NEUROLOGY 75- (23) 2138 -2138 2010/12
- S. Kono; T. Nishio; Y. Takahashi; N. Goto-Inoue; M. Kinoshita; N. Zaima; H. Suzuki; A. Fukutoku-Otsuji; M. Setou; H. Miyajima EUROPEAN JOURNAL OF NEUROLOGY 17- 527 -527 2010/09
- 静脈逆流の影響を受けた大伏在静脈壁脂質分子の挙動田中 宏樹; 海野 直樹; 山本 尚人; 相良 大輔; 鈴木 実; 西山 元啓; 眞野 勇記; 佐野 真規; 斉藤 貴明; 井田 艶子; 岡田 晴子; 兼子 由美; 波多野 絹江; 財満 信宏; 瀬藤 光利 脈管学 50- (Suppl.) S275 -S275 2010/09
- 質量顕微鏡法によるヒト脳脂質の分子イメージング(Molecular imaging of lipids in the human brain by mass spectrometry)由木 大; 財満 信宏; 杉浦 悠毅; 赤津 裕康; 橋詰 良夫; 山本 孝之; 藤原 正美; 杉山 圭吉; 瀬藤 光利 神経化学 49- (2-3) 689 -689 2010/08
- MSの新展開 質量顕微鏡による血管壁構造の観察田中 宏樹; 財満 信宏; 海野 直樹; 瀬藤 光利 JSBMS Letters 35- (Suppl.) 37 -37 2010/08
- 早坂孝宏; 井上菜穂子; 財満信宏; SHRIVAS Kamlesh; 柏木行康; 山本真理; 中許昌美; 瀬藤光利 質量分析総合討論会講演要旨集 58th- 246 2010/06
- 一次性下肢静脈瘤における大伏在静脈の質量顕微鏡法による観察田中 宏樹; 海野 直樹; 山本 尚人; 相良 大輔; 鈴木 実; 西山 元啓; 眞野 勇記; 佐野 真規; 財満 信宏; 瀬藤 光利 静脈学 21- (2) 179 -179 2010/05
- Autogenous Arteriovenous Graftの質量顕微鏡法による観察田中 宏樹; 海野 直樹; 山本 尚人; 相良 大輔; 鈴木 実; 西山 元啓; 眞野 勇記; 佐野 真規; 財満 信宏; 瀬藤 光利 日本血管外科学会雑誌 19- (2) 407 -407 2010/04
- 田中 宏樹; 海野 直樹; 山本 尚人; 相良 大輔; 鈴木 実; 西山 元啓; 眞野 勇記; 佐野 真規; 財満 信宏; 佐々木 健; 瀬藤 光利 日本外科学会雑誌 111- (臨増2) 247 -247 2010/03
- 由木大; 杉浦悠毅; 財満信宏; 瀬藤光利 実験医学 28- (20) 2010
- Dai Yuki; Nobuhiro Zaima; Yuki Sugiura; Hiroyasu Akatsu; Yosio Hashizume; Takayuki Yamamoto; Masami Fujiwara; Keikichi Sugiyama; Mitsutoshi Setou NEUROSCIENCE RESEARCH 68- E333 -E333 2010
- 財満信宏; 杉浦悠毅; 杉浦悠毅; 平野賢一; 大熊彩; 岡橋里美; 野口悟; 西野一三; 衣斐達; 佐橋功; 瀬藤光利; 瀬藤光利 質量分析総合討論会講演要旨集 57th- 2009
- ミオパチー生検筋の質量分析顕微鏡を用いた多変量解析衣斐 達; 小澤 史子; 佐橋 功; 財満 信宏; 杉浦 悠毅; 瀬藤 光利; 西野 一三 臨床神経学 48- (12) 1118 -1118 2008/12 [Refereed]
- 直接質量分析装置の疾患組織解析への応用財満 信宏; 杉浦 悠毅; 大熊 彩; 岡橋 里美; 野口 悟; 西野 一三; 衣斐 達; 小澤 史子; 佐橋 功; 瀬藤 光利 JSBMS Letters 33- (Suppl.) 85 -85 2008/08 [Refereed]
- 財満信宏; 杉浦悠毅; 大熊彩; 岡橋里美; 野口悟; 西野一三; 衣斐達; 小澤史子; 佐橋功; 瀬藤光利; 瀬藤光利 質量分析総合討論会講演要旨集 56th- 2008
- 財満信宏; 財満信宏; 杉浦悠毅; 平野賢一; 大熊彩; 岡橋里美; 野口悟; 西野一三; 衣斐達; 佐橋功; 瀬藤光利; 瀬藤光利 日本油化学会年会講演要旨集 47th- 2008
- 佐橋功; 衣斐達; 衣斐達; 小澤史子; 財満信宏; 杉浦悠毅; 瀬藤光利; 瀬藤光利; 西野一三 筋ジストロフィーおよびその関連する疾患の病態生理の解明と治療薬物の開発に関する研究 清水班 平成17-19年度研究報告書 2008
Books and other publications
- 栄養素でわかる食品と健康=WEB連動テキスト財満信宏 (Contributor)培風館 2016/04
- Encyclopedia of Analytical Chemistry.Nobuhiro Zaima (Joint work)John Wiley & Sons, Ltd 2015/09
- 平田 孝; 菅原 達也; 又平 芳春; 酒井 祥太; 都築 毅; 宮澤 陽夫; 橋本 道男; 財満 信宏; 齋藤 洋昭; 眞岡 孝至; 水田 尚志; 日本水産学会; 平田 孝; 菅原 達也 恒星社厚生閣 2011/10 4769912595 130
- Imaging Mass SpectrometryNobuhiro Zaima (Joint work)Springer 2010/01
- 質量顕微鏡法財満信宏 (Joint work)シュプリンガージャパン株式会社 2008/11
- PharmacologyNobuhiro Zaima (Joint work)
Lectures, oral presentations, etc.
- 大豆サポニンアグリコン(ソヤサポゲノール)の脂肪細胞における脂肪蓄積への影響 [Not invited]髙田祐一; 加茂修一; 岩本和子; 川畑葉月; 財満信宏; 佐藤俊郎; 森山達哉第1回中性脂肪学会学術集会 2017/09
- 脂肪分の過剰摂取がAAAに与える影響 [Not invited]橋本佳祐; 久後裕菜; 宮本智絵; 財満信宏; 森山達哉第1回中性脂肪学会学術集会 2017/09
- 高シュークロース食の摂取が腹部大動脈瘤の進展・破裂と血管壁に出現する脂肪細胞へ及ぼす影響の病理的評価 [Not invited]宮本 智絵; 橋本 佳祐; 久後 裕菜; 財満 信宏; 森山 達哉第1回中性脂肪学会学術集会 2017/09
- 腹部大動脈瘤血管壁における脂肪細胞出現機構の解明 [Not invited]久後 裕菜; 財満 信宏; 森山 達哉第1回中性脂肪学会学術集会 2017/09
- 卵巣摘出(OVX)マウスにおける脂質代謝関連因子に及ぼすTaheebo (Tabebuia avellanedae Lorentz ex Griseb) 抽出物の影響の評価 [Not invited]岩本和子; 福田陽一; 土岐倉千智; 野田真祐子; 山本彩実; 山本美里; 山下光明; 財満信宏; 飯田彰; 森山達哉第1回中性脂肪学会学術集会 2017/09
- 腹部大動脈瘤破裂と TG の関係 [Invited]財満信宏第1回 中性脂肪学会学術集会 2017/09
- 食な新たなリスク:花粉症に関連する新規な食物アレルギー [Not invited]花房佳世; 植田啄也; 村上浩規; 矢野えりか; 財満信宏; 森山達哉アグリバイオ 2017/08
- 中性脂肪蓄積心筋血管症における冠動脈硬化の病理学的特徴と画像との対比 [Not invited]池田善彦; 平野賢一; 財満信宏; 東将浩日本動脈硬化学会総会・学術集会プログラム・抄録集(Web) 2017/06
- 腹部大動脈瘤の破裂機構の解明と破裂予防法の検討 [Not invited]財満信宏; 久後裕菜; 田中宏樹; 柳本賢一; 佐々木健; 浦野哲盟; 海野直樹; 森山達哉脂質生化学研究 2017/06
- 血管壁に異常出現した脂肪細胞が腹部大動脈瘤破裂を誘導する [Not invited]久後裕菜; 財満信宏; 田中宏樹; 毛利陽平; 柳本賢一; 佐々木健; 浦野哲盟; 海野直樹; 森山達哉第71回日本栄養・食糧学会 2017/05
- 高シュークロース食摂取による腹部大動脈瘤の進展・破裂への影響評価 [Not invited]宮本智絵; 橋本佳祐; 久後裕菜; 財満信宏; 森山達哉第71回日本栄養・食糧学会 2017/05
- エラグ酸がアディポサイトカイン類とリポタンパク質の分泌に及ぼす効果 [Not invited]家田彩菜; 直江美咲; 奥野悠子; 岩本和子; 財満信宏; 森山達哉第71回日本栄養食糧学会 2017/05
- 質量分析イメージングによるアントシアニン分子種のマウス体内動態解析 [Not invited]山田周平; 財満信宏; 荘厳哲哉; 森山達哉第71回日本栄養・食糧学会 2017/05
- 卵巣摘出 (OVX) マウスにおけるTaheebo (Tabebuia avellanedae Lorentz ex Griseb) 抽出物の抗肥満効果とその作用物質の同定 [Not invited]岩本和子; 福田陽一; 土岐倉千智; 野田真祐子; 山本彩実; 山本美里; 山下光明; 財満信宏; 飯田彰; 森山達哉第71回日本栄養・食糧学会 2017/05
- マウスモデル系を用いた卵白タンパク質の経皮感作条件の検討 [Not invited]小川昂志; 高葢秋穂; 村上浩規; 岩本和子; 矢野えりか; 財満信宏; 森山達哉第71回日本栄養・食糧学会 2017/05
- マウスモデル系を用いたソバタンパク質の経皮感作に関する研究 [Not invited]高葢秋穂; 村上浩規; 小川昂志; 岩本和子; 矢野えりか; 財満信宏; 森山達哉第71回日本栄養・食糧学会 2017/05
- 大豆サポニンアグリコン(サポゲノール)の脂肪細胞機能に及ぼす影響 [Not invited]髙田祐一; 加茂修一; 岩本和子; 川畑葉月; 財満信宏; 佐藤俊郎; 森山達哉第71回日本栄養・食糧学会 2017/05
- マウスを用いた卵白タンパク質の経皮感作モデル系の確立と高度化 [Not invited]小川昂志; 高葢秋穂; 村上浩規; 岩本和子; 矢野えりか; 財満信宏; 森山達哉日本農芸化学会 2017年度大会 2017/03
- 腹部大動脈瘤の進展・破裂に及ぼす高脂肪食の影響評価 [Not invited]橋本佳祐; 久後裕菜; 財満信宏; 森山達哉日本農芸化学会2017年度京都大会 2017/03
- マウスを用いた卵白タンパク質の経皮感作モデル系の確立と高度化 [Not invited]小川昂志; 高葢秋穂; 村上浩規; 岩本和子; 矢野えりか; 財満信宏; 森山達哉日本農芸化学会大会講演要旨集(Web) 2017/03
- キノコに含まれるシリンガ酸はエストロゲンレセプター非依存的に骨粗鬆症モデルマウスの骨密度減少を抑制する [Not invited]田中照佳; 川口信久; 財満信宏; 森山達哉; 福田泰久; 白坂憲章日本農芸化学会大会講演要旨集(Web) 2017/03
- 腹部大動脈瘤の進展・破裂に及ぼす高脂肪食の影響評価 [Not invited]橋本佳祐; 久後裕菜; 財満信宏; 森山達哉日本農芸化学会大会講演要旨集(Web) 2017/03
- セサミン・セサモリンの脳内移行におよぼすウコン由来ターメロン高含有画分の影響 [Not invited]松村 晋一; 吉岡 百合; 財満 信宏; 森本 正則; 村田 和也; 松田 秀秋日本薬学会年会要旨集 2017/03
- 高葢秋穂; 村上浩規; 三口志穂; 矢野えりか; 岩本和子; 財満信宏; 森山達哉月刊アレルギーの臨床 2017/02保存性が高く植物界に広く分布する汎アレルゲンは、全身症状や花粉症に関連したOASなどを引き起こす。汎アレルゲンの1つであるソーマチンライクプロテイン(PR-5)は、花粉にも含まれるが、OASを中心とした症状を惹起するのか、あるいは経腸的に吸収されて全身症状を惹起するのかいまだ十分に解明されていない。そこで、本研究ではサクランボやチェリーに含まれるソーマチンライクプロテイン(Pru av2)の特性を多様な観点から評価した。さらに、近年問題となっている新たな感作経路である経皮感作を起こしうるのかをマウスを用いて検討した。(著者抄録)
- Adipocyte in vascular wall can induce the rupture of abdominal aortic aneurysm [Not invited]Hirona Kugo; Nobuhiro Zaima; Hiroki Tanaka; Youhei Mouri; Kenichi Yanagimoto; Kohsuke Hayamizu; Keisuke Hashimoto; Takeshi Sasaki; Masaki Sano; Tatsuro Yata; Tetsumei Urano; Mitsutoshi Setou; Naoki Unno; Tatsuya Moriyama第24回日本血管生物医学会学術集会 2016/12
- 経口免疫寛容によって大豆タンパク質の経皮感作が抑制される [Not invited]村上浩規; 高葢秋穂; 小川昂志; 矢野えりか; 財満信宏; 森山達哉2016/10
- 腹部大動脈瘤の進展・破裂に及ぼす高脂肪食の影響評価 [Not invited]橋本佳祐; 久後裕菜; 財満信宏; 森山達哉2016/10
- 腹部大動脈瘤の新規モデル動物の作出とその病理解析 [Not invited]宮本智絵; 橋本佳祐; 久後裕菜; 田中 宏樹; 海野直樹; 財満信宏; 森山達哉2016/10
- 植物汎アレルゲンであるソーマチンライクプロテイン(PR-5)の特性解析 [Not invited]高葢秋穂; 三口志穂; 小川昂志; 村上浩規; 矢野えりか; 財満信宏; 森山達哉日本栄養・食糧学会 第55回近畿支部大会 2016/10
- 経皮感作される卵白タンパク質の解析 [Not invited]小川昂志; 高葢秋穂; 村上浩規; 矢野えりか; 財満信宏; 森山達哉日本栄養・食糧学会 第55回近畿支部大会 2016/10
- マウス眼球及び周囲組織におけるアントシアニン分子種の動態解析 [Not invited]山田周平; 荘厳哲哉; 財満信宏; 森山達哉日本栄養・食糧学会 第55回近畿支部大会 2016/10
- The effect of high fat diet on development of abdominal aortic aneurysm [Not invited]Keisuke Hashimoto; Hirona Kugo; Nobuhiro Zaima; Tatsuya Moriyama2016/10
- The effect of dietary food on the development of abdominal aortic aneurysm [Not invited]Hirona Kugo; Nobuhiro Zaima; Youhei Mouri; Hiroki Tanaka; Kenichi Yanagimoto; Tetsumei Urano; Naoki Unno; Tatsuya MoriyamaThe 1st Joint Meeting of ISFP and PA Workshop 2016/10
- ウコン精油のβ-セクレターゼ阻害作用 [Not invited]松村 晋一; 村田 和也; 吉岡 百合; 財満 信宏; 森本 正則; 岩城 正宏; 松田 秀秋日本生薬学会年会講演要旨集 2016/08
- 食品による疾患の予防 [Invited]財満信宏近畿大学農学部 公開講座 2016/05
- 腹部大動脈瘤発症に対する魚油の予防効果の検討 [Not invited]久後裕菜; 財満信宏; 毛利陽平; 田中宏樹; 柳本賢一; 浦野哲盟; 海野直樹; 森山達哉第70回 日本栄養・食糧学会 2016/05
- ヒト腹部大動脈瘤の病理解析と新規モデル動物の作出 [Not invited]財満信宏; 久後裕菜; 田中宏樹; 海野直樹; 森山達哉第70回 日本栄養・食糧学会 2016/05
- 低アレルゲン性新規食品素材としての大豆ホエイの特性解析 [Not invited]植田啄也; 和田宏章; 矢野えりか; 石黒貴寛; 村澤久司; 小川正; 財満信宏; 森山達哉第70回 日本栄養・食糧学会 2016/05
- 経皮感作し得る大豆タンパク質の検出及び同定 [Not invited]村上浩規; 小川祥平; 矢野えりか; 財満信宏; 森山達哉第70回 日本栄養・食糧学会 2016/05
- 虫害被害を受けた大豆(枝豆)のプロテオノーム・アレルゲノーム解析 [Not invited]花房佳世; 矢野えりか; 末森祐輔; 財満信宏; 森山達哉第70回 日本栄養・食糧学会 2016/05
- 低アレルゲン性新規食品素材としての大豆ホエイの特性解析 [Not invited]植田 啄也; 和田 宏章; 矢野 えりか; 石黒 貴寛; 村澤 久司; 小川 正; 財満 信宏; 森山 達哉日本栄養・食糧学会大会講演要旨集 2016/04
- 経皮感作し得る大豆タンパク質の検出及び同定 [Not invited]村上 浩規; 小川 祥平; 矢野 えりか; 財満 信宏; 森山 達哉日本栄養・食糧学会大会講演要旨集 2016/04
- 虫害被害を受けた大豆(枝豆)のプロテオーム・アレルゲノーム解析 [Not invited]花房 佳世; 矢野 えりか; 末森 佑輔; 財満 信宏; 森山 達哉日本栄養・食糧学会大会講演要旨集 2016/04
- お米の栄養はどこにある?目に見えない分子を可視化する技術ー質量分析イメージングの原理と実際- [Invited]財満信宏機能性健康米協会シンポジウム 2016/02
- 食品による疾患の予防 [Invited]財満信宏近畿大学農学部 公開講座 2015/10
- アントシアニンの体内動態解析 [Not invited]財満信宏; 稲葉栞里; 藤森隆道; 荘厳哲哉; 小林沙織; 森山達哉第40回日本医用マススペクトル学会年会 2015/09
- 経皮感作し得る大豆タンパク質の特性解析 [Not invited]村上浩規; 小川祥平; 和田宏章; 末森祐輔; 矢野えりか; 財満信宏; 森山達哉日本食品科学工学会 第62回大会 2015/08
- The preventive effect of fish oil on the development of abdominal aortic aneurysm [Not invited]Hirona Kugo; Youhei Mouri; Ken-ichi Yanagimoto; Nobuhiro Zaima; Tatsuya Moriyama12th Asian Congress of Nutrition 2015/05
- Characteristic Distribution of Metabolites in Oryza sativa Rice [Not invited]Nobuhiro Zaima; Yukihiro Yoshimura; Yukio Kawamura; Tatsuya Moriyama106th AOCS Annual Meeting 2015/05
- 新精米法による新たな機能性米の創出とその機能成分の可視化 [Not invited]財満信宏; 郡俊之; 森山達哉; 川西孝彦; 寺下隆夫; 白坂憲章日本農芸化学会2015年度大会 2015/03
- イメージングマススペクトロメトリーの原理と分析事例 [Invited]財満信宏第45回中部化学関連学協会連合秋季大会 2014/11
- 悪玉アディポサイトカインであるレジスチンの変動解析の再検討 [Not invited]山本美里; 田前 諒; 山中大輔; 矢野えりか; 末森祐輔; 鵜澤有希; 財満信宏; 森山達哉日本栄養・食糧学会 第53回近畿支部大会 2014/10
- Nicotine投与がラット腹部大動脈血管壁に及ぼす影響の評価 [Not invited]久後裕菜; 財満信宏; 森山達哉日本栄養・食糧学会 第53回近畿支部大会 2014/10
- 農作物の収穫後処理による汎アレルゲンの変動解析 [Not invited]三口志穂; 矢野喜裕; 矢野えりか; 末森祐輔; 鵜澤有希; 財満信宏; 小川 正; 森山達哉日本栄養・食糧学会 第53回近畿支部大会 2014/10
- イメージングマススペクトロメトリー(IMS)による卵黄脂質層構造の解析 [Not invited]東埜恭明; 財満信宏; 森山達哉日本栄養・食糧学会 第53回近畿支部大会 2014/10
- イメージングマススペクトロメトリーによる食品機能研究 [Not invited]財満 信宏; 森山達哉第59回食品新素材研究会 2014/09
- 中性脂肪蓄積心筋血管症患者由来繊維芽細胞のTG代謝に及ぼすカルニチンの影響 [Not invited]須見友子; 鵜澤有希; 平野賢一; 財満信宏; 森山達哉日本油化学会 2014/09
- イメージング質量分析の食品科学への応用 [Invited]財満信宏第41回BMSコンファレンス 2014/07
- イメージングマススペクトロメトリーによるスフィンゴ脂質の可視化 [Invited]財満信宏日本農芸化学会2014年度大会シンポジウム 2014/03
- 腹部大動脈瘤発症に及ぼすn-3系高度不飽和脂肪酸の影響評価 [Not invited]久後裕菜; 毛利陽平; 柳本賢一; 韓力; 財満信宏; 森山達哉日本農芸化学会 2014/03
- イメージングマススペクトロメトリーによる脂質の可視化 [Invited]財満信宏健康・長寿談話会 2013/11
- イメージングマススペクトロメトリーによる機能性食品成分の可視化 [Not invited]財満信宏メタボロームシンポジウム 2013/10
- 凍り豆腐の大豆クラス2アレルギーリスク低減化 の実証 [Not invited]和田宏章; 末森祐輔; 矢野えりか; 財満信宏; 石黒貴寛; 村澤久司; 小川正; 森山達哉; 河村幸雄日本栄食・食糧学会 第52回近畿支部大会 2013/10
- 豆味噌抽出物による破骨細胞分化抑制効果 [Not invited]土岐倉千智; 木村裕; 田中照佳; 鵜澤有希; 財満信宏; 森山達哉; 河村幸雄日本栄食・食糧学会 第52回近畿支部大会 2013/10
- 中性脂肪蓄積心筋血管症患者由来繊維芽細胞の脂質代謝に及ぼすカルニチンの影響 [Not invited]須見友子; 鵜澤有希; 平野賢一; 財満信宏; 森山達哉; 河村幸雄日本栄食・食糧学会 第52回近畿支部大会 2013/10
- 大豆サポニンアグリコン(ソヤサポゲノール)の脂肪細胞分化抑制効果 [Not invited]小林知世; 境野眞善; 山下貴稔; 加茂修一; 佐藤俊郎; 財満信宏; 森山達哉; 河村幸雄日本栄食・食糧学会 第52回近畿支部大会 2013/10
- イメージングマススペクトロメトリー-質量分析で脂質を見る- [Invited]財満信宏日本油化学会 2013/09
- 肥満・糖尿病モデルマウスに対する大豆サポニンの抗肥満効果 [Not invited]小林知世; 境野眞善; 山下貴稔; 加茂修一; 佐藤俊郎; 財満信宏; 森山達哉; 河村幸雄第60回日本食品科学工学会大会 2013/08
- 新規大豆食品素材(大豆ペースト)の低アレルゲン性及び消化性の解析 [Not invited]森山達哉; 山田陽子; 矢野えりか; 崎川貴文; 末森祐輔; 財満信宏; 片岡雅人; 長瀬二郎; 河村幸雄第60回日本食品科学工学会大会 2013/08
- Ba-8 wx/ae二重変異体米の澱粉吸着型リゾホスファチヂルコリンの定量と胚乳部における局在解析(澱粉の構造・物性・利用,一般講演,日本応用糖質科学会平成25年度大会(第62回)) [Not invited]庄野 陽祐; 小谷口 美也子; 藤原 美乃里; 中屋 慎; 財満 信宏; 北村 進一応用糖質科学 : 日本応用糖質科学会誌 2013/08
- IMSによる組織内代謝変動の可視化-食品成分動態解析と病理解析への応用- [Invited]財満信宏日本農芸化学会2013年度大会シンポジウム 2013/03
- メタボローム可視化の生命科学への応用 [Invited]財満信宏生命医薬情報学連合大会 2012/10
- ヒト腹部大動脈瘤の病理解析とモデル動物の新規作出 [Not invited]毛利陽平; 財満信宏; 田中宏樹; 森山達哉; 河村幸雄; 海野直樹; 瀬藤光利日本食品科学工学会2012年度大会 2012/08
- 脂肪細胞からのレジスチン分泌を抑制する食品成分の探索 [Not invited]若木泰子; 吉村征浩; 鵜澤有希; 財満信宏; 森山達哉; 河村幸雄第29回日本微量栄養素学会学術集会 2012/06
- クロマグロ皮たんぱく質経口摂取によるマウスの肝機能保護作用 [Not invited]髙橋賢次; 田中照佳; 岩本直樹; 阿川泰夫; 澤田好史; 吉村征浩; 財満信宏; 森山達哉; 河村幸雄日本農芸化学大会 2012/03
- ザクロ抽出物およびエラグ酸によるタンパク質分解亢進を介したレジスチン分泌抑制効果 [Not invited]若木泰子; 吉村征浩; 鵜澤有希; 財満信宏; 森山達哉; 河村幸雄日本農芸化学会大会 2012/03
- 新規の腹部大動脈瘤モデルラットの作出と病理解析 [Not invited]毛利陽平; 財満信宏; 田中宏樹; 森山達哉; 河村幸雄; 海野直樹; 瀬藤光利日本農芸化学会2012年度大会 2012/03
- 経口摂取プエラリンのマウス骨吸収抑制作用と大腿骨への移行 [Not invited]田中照佳; 吉村征浩; 道原成和; 山本彩実; 財満信宏; 森山達哉; 河村幸雄日本農芸化学大会 2012/03
- IMSによるプエラリンの体内動態解析 [Not invited]山本彩実; 財満信宏; 吉村征浩; 田中照佳; 森山達哉; 河村幸雄日本農芸化学大会 2012/03
- IMS解析が明らかにするアントシアニンの分子種による組織内局在の違い [Not invited]吉村征浩; 財満信宏; 森山達哉; 河村幸雄日本農芸化学大会 2012/03
- イメージングマススペクトロメトリーによる農作物の機能性食品成分の局在解析 [Not invited]財満信宏; 吉村征浩; 森山達哉; 河村幸雄日本農芸化学大会 2012/03
- 田中 宏樹; 海野 直樹; 山本 尚人; 相良 大輔; 鈴木 実; 西山 元啓; 眞野 勇記; 佐野 真規; 財満 信宏; 佐々木 健; 瀬藤 光利日本外科学会雑誌 2010/03
- OP-241 腎癌の脂質プロファイリング(腎腫瘍/基礎2,一般演題口演,第98回日本泌尿器科学会総会) [Not invited]高山 達也; 財満 信宏; 宮崎 美紀; 高岡 直央; 京野 陽子; 伊藤 寿樹; 杉山 貴之; 永田 仁夫; 古瀬 洋; 栗田 豊; 麦谷 荘一; 瀬藤 光利; 大園 誠一郎日本泌尿器科学会雑誌 2010
Research Themes
- 日本学術振興会:科学研究費助成事業Date (from‐to) : 2022/04 -2026/03Author : 細野 崇; 榎元 廣文; 財満 信宏
- 日本学術振興会:科学研究費助成事業Date (from‐to) : 2021/04 -2025/03Author : 井上 菜穂子; 財満 信宏; 古市 泰郎骨格筋は体を動かす動的な役割を担うだけでなく、体内の70%の糖を代謝する重要な糖代謝器官である。疾患や加齢に伴い筋量が減少することから、有効的な筋肥大メカニズムの解明、および筋萎縮を抑制するような薬剤等が期待されている。骨格筋が肥大するには、組織内に存在する幹細胞が増殖して、筋線維に融合するプロセスが必要になる。そこで本研究では細胞膜の融合イベントに注目することとした。すでに、筋細胞が融合する際に必須の融合制御タンパク質が同定されており、いずれも細胞膜脂質の一種であるホスファチジルセリンを認識・制御する因子であった。しかし、これまでホスファチジルセリンが関与することは報告されてきたものの、ホスファチジルセリンの中でどのような分子種が融合に関与しているか、という解析はなされていない。我々は、ホスファチジルセリンの分子種組成には細胞特異性が存在し、特定の分子種が膜タンパク質との結合能に寄与しているのではないか、と考え、筋肥大に必要な筋細胞の融合メカニズムを明らかにすることを目的として、研究を行うこととした。初年度は、筋肥大誘導動物モデルとして、持久的運動トレーニングを行ったマウスを作成し、腓腹筋を対象として変動のある脂質分子種の探索を行った。その結果、肥大に伴い変動する脂質分子の同定を達成した。さらに筋萎縮動物モデルとして、ギプス固定による廃用性筋萎縮モデルを作出し、その際に変動する脂質分子種の選定も行った。これらの脂質分子はいずれもホスファチジルセリンを含む細胞膜構成脂質であり、骨格筋細胞の融合イベントに関与する分子である可能性があるため、今後詳細な機能解析を進めていく予定である。
- Japan Society for the Promotion of Science:Grants-in-Aid for Scientific ResearchDate (from‐to) : 2021/04 -2025/03Author : 財満 信宏本研究は腹部大動脈瘤の進展や破裂に至る病理学的機序の理解と、病態の進展や破裂を予防するための方法を確立することを目的としたものである。 病理学的機序の解析:これまでに報告された研究により腹部大動脈瘤の終末段階の病態の理解が進んだ一方で、初期から終末像に至る病態遷移には不明な点が多く存在した。特に初期病態の理解は、腹部大動脈瘤の予防標的明確化に重要な意味を持つため、我々が確立したモデルの経時的病態解析を行った。その結果、初期に変動する因子が明らかになったほか、病態が大きく分けて5段階あることなどを見出した(Biology 2021)。また、ヒト腹部大動脈瘤終末像に特徴的に観察される脂肪細胞の出現を培養細胞で再現し、脂肪細胞の機能変化に関与する可能性のあるシグナル伝達系を報告した(Adipocyte 2021)。 進展・破裂予防法:エイコサペンタエン酸(EPA)は腹部大動脈瘤進展を抑制する可能性があることが報告されているが、瘤壁のどこに存在するかは不明であった。モデル動物を用いて質量分析イメージングでEPAの動態を解析した結果、EPAは瘤壁でM2マクロファージに選択的に取り込まれている可能性があることを見出した(Food & Funct. 2021)。この結果はヒトでも同様の結果である可能性を発見している(J. Lipid Res. 2022)。また、これまでの研究によって、高脂肪食と高シュークロース食は腹部大動脈瘤の進展に及ぼす影響が異なる可能性をモデル動物で見出した。この原因が血管周囲脂肪組織への影響の違いによって説明できる可能性があることを報告した(Adipocyte 2021)。
- Japan Society for the Promotion of Science:Grants-in-Aid for Scientific ResearchDate (from‐to) : 2021/07 -2024/03Author : 財満 信宏我々は無数の香気成分に囲まれて生活している。ある種の香気成分は、微量でも嗅覚受容体などを介して生理機能を発揮することはよく知られているが、嗅覚通過後の香気成分の体内動態や代謝・生理機能については不明な点が多い。この研究課題を申請する際、いくつかの香気成分が吸入後に体内に蓄積する可能性を見出していた。この観察結果は、香気成分が体内移行し、何らかの形で生命活動に影響を及ぼすことを示唆するものであり、本研究ではこの基礎的知見を得ることを目的とした。マウスに何種類かの香気成分を含む精油を吸引させた結果、βカリオフィレンが未変化体のまま体内移行し、肝臓代謝に影響を及ぼすことを明らかにした(Sci. Rep. 2021)。また、ウコンに含まれるターメロン類も未変化体のまま体内移行することを報告した(Food Biosci. 2021)。また、構造によって、体内移行の特徴が異なることも見出した。これらの発見は、香りと生命活動の間の未知なる関係が存在することを示すものであり、基礎的な知見の集積が必要であることを示す。今後、体内移行機序及び生命活動に及ぼす影響を評価する。
- 日本学術振興会:科学研究費助成事業 基盤研究(C)Date (from‐to) : 2020/04 -2023/03Author : 佐々木 健; 財満 信宏; 佐野 真規腹部大動脈瘤(AAA)は進行性の大動脈疾患であり、最終的に破裂すると高い死亡率に至る。大動脈をはじめとする血管には血管周囲脂肪組織が存在し、そこには多数の脂肪細胞(血管周囲脂肪細胞:perivascular adipocyte: PAC)が含まれる。我々の研究では、このAAA病変のPACは過剰に脂質を取り込んで悪玉化しており、炎症性のサイトカインを高発現していることを見出した。さらにこれらのPACが存在するAAAの外膜領域において、様々な炎症細胞の高度な浸潤が認められた。一方、大動脈をはじめとする血管には血管内血管や血管内リンパ管が存在し、その血管壁における様々な分子や細胞(炎症細胞など)の運搬を担っていると考えられている。 前年度までの研究で、我々は、AAA病変におけるその血管内血管の変化についても調べたところ、外膜境界域で血管内血管は巨大化し、血管内皮細胞で細胞間接着分子の低下や内皮細胞自身のアポトーシスが認められ、さらに出血様の病理所見も多数観察されたことから、AAAにおける血管内血管の脆弱化が示唆された。 一方で動脈硬化巣と同様に、大動脈瘤病変の内膜にも血管内血管が存在していることが知られている。本年度はこの内膜の血管内血管について検討を加えた。その結果、内膜内では血管内血管が増加し、それらは外膜の血管内血管と接続していたため、外膜より延伸してきた血管内血管であることが考えられた。またこの内膜内の血管内血管は病変の進行により増加することも示された。以上のことから、この血管内血管の変化は、大動脈瘤における炎症に起因する血管新生因子によることが予想され、大動脈瘤の進展に関与する可能性が考えられた。
- Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)Date (from‐to) : 2017/04 -2021/03Author : zaima nobuhiroAbdominal aortic aneurysm is a vascular disease with silent graduation of abdominal aorta. Several previous studies suggested that dietary habits affect the development of abdominal aortic aneurysm. However, the relationship between dietary habits and abdominal aortic aneurysm are clearly unknown. In this study, we found several food factors which have pro-aneurysm and anti-aneurysm effect. In addition, we reported mechanisms of action of the food factors. These findings provide important basic evidence to develop method of preventing abdominal aortic aneurysm.
- 腹部大動脈瘤の進展・破裂予防法の確立文部省科学研究費 (基盤研究B)Date (from‐to) : 2017 -2020Author : 財満信宏
- Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory ResearchDate (from‐to) : 2016/04 -2019/03Author : Zaima NobuhiroAtherosclerosis is a basic predisposition to several major diseases. Deposition of cholesterol ester is one of pathological features of atherosclerosis. We previously found a new atherosclerotic lesion with deposition of triglyceride, not but cholesterol ester. We named the abnormal disease condition as triglyceride deposit cardiomyovasculopathy (TGCV). At present, it is difficult to distinguish between atherosclerosis and TGCV. In this study, we aimed to establish new method to distinguish atherosclerosis and TGCV by using spectral imaging.
- 分光イメージング法による脂質の選択的可視化文部省科学研究費 (挑戦的萌芽)Date (from‐to) : 2016/04 -2019/03Author : 財満信宏
- Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (A)Date (from‐to) : 2013/04 -2017/03Author : ZAIMA NobuhiroMass microscopy (mass spectrometry imaging : MSI) is a method to visualize the spatial distribution of molecules in tissue section. This new method will provide important findings for the pathological examination. However, there is some limitations to apply this method to pathological examination. In this study, we establish a new method to enhance the sensitivity and specificity of MSI. In addition, we clarified the pathological meaning of data obtained from MSI analysis of biological samples.
- Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory ResearchDate (from‐to) : 2013/04 -2016/03Author : ZAIMA NobuhiroIt is well known that functional food factors have the preventive effect on the diseases. There are several studies on the action mechanism of the functional food factors. However, the research method to investigate the dynamics of functional food factor remains to be established. Because the information provides important clues to clarify the action mechanism of the functional food factors, we aim to establish the research method to investigate the dynamics of functional food factors using mass spectrometry imaging.
- 質量顕微鏡を用いた新規疾患解析手法の実用性の検討文部省科学研究費 (基盤研究C)Date (from‐to) : 2010/04 -2013/03Author : 財満信宏
- 高品質な農林水産物・食品創出のための質量顕微鏡技術基盤の構築生物系特定産業技術研究支援センター:イノベーション創出基礎的研究推進事業Date (from‐to) : 2009/04 -2012/03Author : 財満信宏
- Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)Date (from‐to) : 2010 -2012Author : ZAIMA NobuhiroThe aim of this study is to enhance utility of imaging mass spectrometry (IMS) as new pathophysiological examination. IMS is a two-dimensional MS technique used to visualize the spatial distribution of biomolecules without extraction, purification, separation, or labeling of biological samples. It is important to estimate general versatility of IMS. In this study, we try to visualize the metabolic variation of diseases, including ATGL mutant disease, atherosclerosis, and abdominal aortic aneurysm. We succeed to find some characteristic changes in disease tissues by using IMS.
- Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research a proposed research project)Date (from‐to) : 2009 -2011Author : MATSUZAKI Hideo; ZAIMA Nobuhiro; IWATA Keiko; OGAWA Mikako; TSUJII Masatsugu; SETOU Mitsutoshi; TSUCHIYA Kenji; ITOH Hiroaki; MAGATA YasuhiroIn this project, we were focusing on impaired Very Low Density Lipoprotein (VLDL) lipid fraction in serum of individuals with autism. Then, we examined the serum levels of fatty acid composition, autistic animal models based on the lipid profile, imaging analyze and a novel therapy method of autism by using the autistic animal model. To identify causal fatty acid of VLDL-specific lipid profile in autism, we analyzed fatty acid composition by GC-MS, which resulted in impairment of some fatty acids including omega-6. Next, we identified that CD38KO mice showed impairment of VLDL fraction and omega-6 fatty acid like autistic human subject, and found that feeding challenge of omega-6 fatty acid could rescue impairment of social recognition behavior in CD38KO mice immediately after birth. In VLDL Receptor transgenic rat (VLDLR-Tg), we examined behavior test and found that the rat showed hyperactivity and an entire impairment of arachidonic acid distribution in tissues of VLDLR-Tg.
- 質量顕微分析を用いた疾患組織検査方法の確立文部科学省科研費 (若手研究B)Date (from‐to) : 2008/04 -2010/03Author : 財満信宏
- Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)Date (from‐to) : 2008 -2009Author : ZAIMA NobuhiroBiochemical approaches, such as staining, are widely used as pathological analysis. These methods are essential for pathological analysis. However, they have some disadvantages. For example, they cannot be applied to non-targeting analysis. Establishment of new pathological method is important to analyze idiopathic disease. In this study, new pathological analysis using imaging mass spectrometry for non-targeting analysis was established.
Industrial Property Rights
- 松▲崎▼ 秀夫, 謝 敏▲かく▼, 財満 信宏, 吉岡 百合 国立大学法人福井大学, 学校法人近畿大学, 稲畑香料株式会社 202403014083576662
- 財満 信宏, 松村 晋一, 吉岡 百合 学校法人近畿大学, 稲畑香料株式会社 202303014378758897
- 財満 信宏, 久後 裕菜, 北野 幹浩, 廣田 益教, 平野 賢一 学校法人近畿大学, 株式会社八代, 国立大学法人大阪大学 202303011314199810
- 特開2023-001102:植物性色素を含有する組成物 2023/01/04財満 信宏, 松村 晋一, 吉岡 百合, 須見 友子, 山田 和哉, 望月 雄斗, 野津 昌史, 小林 崇典 学校法人近畿大学, 稲畑香料株式会社, 三生医薬株式会社 202303007070948230
- 財満 信宏, 松村 晋一, 吉岡 百合, 牧野 祥平 学校法人近畿大学, 稲畑香料株式会社 202203006745231850
- 特開2021-159086:リグナン類化合物と精油と油脂とを含有する組成物 2021/10/11財満 信宏, 松村 晋一, 吉岡 百合, 小林 崇典, 山田 和哉 学校法人近畿大学, 稲畑香料株式会社, 三生医薬株式会社 202103019521735477
- 特開2021-127338:リグナン類化合物を精油に溶解して含有する組成物 2021/09/02財満 信宏, 松村 晋一, 岩本 好平, 牧野 祥平, 吉岡 百合, 南 久美子, 小林 崇典, 山田 和哉 学校法人近畿大学, 稲畑香料株式会社, 三生医薬株式会社 202103020743928905
- 財満 信宏, 松村 晋一, 吉岡 百合 学校法人近畿大学, 稲畑香料株式会社 202103015177302587
- 特許第5810166号:糖尿病性心血管合併症の予防・治療剤 2015/09/18平野 賢一, 安井 洋子, 池田 善彦, 瀬藤 光利, 財満 信宏 国立大学法人大阪大学, 国立研究開発法人国立循環器病研究センター, 国立大学法人浜松医科大学, 興和株式会社 201503018297550357
- WO2015-005393:大動脈瘤の予防または治療剤および容器詰飲食品 2015/01/15財満 信宏, 毛利 陽平, 柳本 賢一, 韓 力 日本水産株式会社, 学校法人近畿大学 201703008544697195
- WO2013-031729:糖尿病性心血管合併症の予防・治療剤 2013/03/07平野 賢一, 安井 洋子, 池田 善彦, 瀬藤 光利, 財満 信宏 国立大学法人大阪大学, 独立行政法人国立循環器病研究センター, 国立大学法人浜松医科大学, 興和株式会社 201503092442322982
- 特開2012-235715:大動脈瘤モデル動物 2012/12/06海野 直樹, 田中 宏樹, 眞野 勇記, 佐野 真規, 財満 信宏, 瀬藤 光利, 佐々木 健 国立大学法人浜松医科大学 201203061928354202
- WO2011-007565:PPARγ阻害剤を用いる動脈瘤の予防および治療 2011/01/20瀬藤 光利, 財満 信宏, 海野 直樹, 田中 宏樹 国立大学法人浜松医科大学 201303020895501645
- 17620406:PHARMACEUTICAL COMPOSITION FOR AORTIC ANEURYSM PROPHYLAXIS AND PROCESSED FOODNobuhiro Zaima, Hirona Kugo, Motohiro Kitano, Yoshinori Hirota, Ken-ichi Hirano
- 17910672:Caryophyllene-containing agent or composition and various applications thereofNobuhiro Zaima, Yuri Yoshioka, Shinichi Matsumura, Kohei Iwamoto, Kazuya Yamada, Takanori Kobayashi
- 特願18250599:COMPOSITION FOR TREATING VASCULAR DISEASE, COMPOSITION FOR REVENTING VASCULAR DISEASE, COMPOSITION FOR TREATING HYPERTENSION, AND COMPOSITION FOR PREVENTING HYPERTENSIONNobuhiro Zaima, Chihiro Kishi, Yuki Takemoto, Shinichi Matsumura, Yuri Yoshioka, Kohei Iwamoto, Shohei Makino, Kazuya Yamada, Takanori Kobayashi
- 18266070:PHARMACEUTICAL COMPOSITION FOR PREVENTION AND TREATMENT OF AORTIC ANEURYSM, AND PROCESSED FOODNobuhiro Zaima, Hirona Kugo, Motohiro Kitano, Yoshinori Hirota, Ken-ichi Hirano