森島 真幸 (モリシマ マサキ)

  • 農学部 食品栄養学科 准教授
Last Updated :2024/04/23

コミュニケーション情報 byコメンテータガイド

  • コメント

    心臓の正常な機能を維持するための食事パターンを探索するために、日々の食生活が心臓のミトコンドリア機能や心機能に及ぼす影響についての研究に取り組んでいます。

研究者情報

学位

  • 博士(栄養学)(徳島大学)

ホームページURL

J-Global ID

プロフィール

  • 平成14年 管理栄養士免許取得

研究キーワード

  • 公衆栄養学   病態生理学   循環器学   応用栄養学   運動習慣   

現在の研究分野(キーワード)

    心臓の正常な機能を維持するための食事パターンを探索するために、日々の食生活が心臓のミトコンドリア機能や心機能に及ぼす影響についての研究に取り組んでいます。

研究分野

  • ライフサイエンス / 栄養学、健康科学 / 公衆栄養学、食環境整備
  • ライフサイエンス / 医療管理学、医療系社会学 / 疫学調査、食物摂取頻度調査
  • ライフサイエンス / 栄養学、健康科学 / 生活習慣、運動意欲
  • ライフサイエンス / 医療薬学 / microRNA, イオンチャネル, 不整脈
  • ライフサイエンス / 生理学 / microRNA, イオンチャネル, 不整脈

経歴

  • 2022年04月 - 現在  近畿大学農学部食品栄養学科准教授
  • 2019年04月 - 2021年03月  近畿大学農学部食品栄養学科講師
  • 2016年04月 - 2019年03月  徳島大学病院糖尿病対策センター特任講師
  • 2017年09月 - 2018年12月  米国・Drexel大学Dept. Pharmacology and Physiology客員研究員
  • 2007年04月 - 2016年03月  大分大学医学部病態生理学講座(旧循環病態制御講座)助教
  • 2006年10月 - 2007年04月  大分大学医学部循環病態制御講座研究支援者
  • 2006年04月 - 2006年09月  大分大学医学部循環病態制御講座(現病態生理学講座)技術補佐員

学歴

  • 2003年04月 - 2006年03月   徳島大学大学院   栄養学研究科   博士後期課程
  • 2001年04月 - 2003年03月   徳島大学大学院   栄養学研究科   博士前期課程

所属学協会

  • 日本栄養改善学会   日本栄養・食糧学会   日本不整脈心電学会   日本病態生理学会   日本神経科学会   日本生理学会   日本糖尿病学会   

研究活動情報

論文

  • Mengyan Wei; Pu Wang; Xiufang Zhu; Masaki Morishima; Yangong Liu; Mingqi Zheng; Gang Liu; Hiroki Osanai; Kenshi Yoshimura; Shinichiro Kume; Tatsuki Kurokawa; Katsushige Ono
    PloS one 18 2 e0280656  2023年 
    Gemcitabine is an antineoplastic drug commonly used in the treatment of several types of cancers including pancreatic cancer and non-small cell lung cancer. Although gemcitabine-induced cardiotoxicity is widely recognized, the exact mechanism of cardiac dysfunction causing arrhythmias remains unclear. The objective of this study was to electrophysiologically evaluate the proarrhythmic cardiotoxicity of gemcitabine focusing on the human rapid delayed rectifier potassium channel, hERG channel. In heterologous hERG expressing HEK293 cells (hERG-HEK cells), hERG channel current (IhERG) was reduced by gemcitabine when applied for 24 h but not immediately after the application. Gemcitabine modified the activation gating properties of the hERG channel toward the hyperpolarization direction, while inactivation, deactivation or reactivation gating properties were unaffected by gemcitabine. When gemcitabine was applied to hERG-HEK cells in combined with tunicamycin, an inhibitor of N-acetylglucosamine phosphotransferase, gemcitabine was unable to reduce IhERG or shift the activation properties toward the hyperpolarization direction. While a mannosidase I inhibitor kifunensine alone reduced IhERG and the reduction was even larger in combined with gemcitabine, kifunensine was without effect on IhERG when hERG-HEK cells were pretreated with gemcitabine for 24 h. In addition, gemcitabine down-regulated fluorescence intensity for hERG potassium channel protein in rat neonatal cardiomyocyte, although hERG mRNA was unchanged. Our results suggest the possible mechanism of arrhythmias caused by gemcitabine revealing a down-regulation of IhERG through the post-translational glycosylation disruption possibly at the early phase of hERG channel glycosylation in the endoplasmic reticulum that alters the electrical excitability of cells.
  • Yan Wang; Masaki Morishima; Katsushige Ono
    Membranes 12 7 2022年07月 
    Two distinct isoforms of the T-type Ca2+ channel, Cav3.1 and Cav3.2, play a pivotal role in the generation of pacemaker potentials in nodal cells in the heart, although the isoform switches from Cav3.2 to Cav3.1 during the early neonatal period with an unknown mechanism. The present study was designed to investigate the molecular system of the parts that are responsible for the changes of T-type Ca2+ channel isoforms in neonatal cardiomyocytes using the whole-cell patch-clamp technique and mRNA quantification. The present study demonstrates that PKC activation accelerates the Ni2+-sensitive beating rate and upregulates the Ni2+-sensitive T-type Ca2+ channel current in neonatal cardiomyocytes as a long-term effect, whereas PKC inhibition delays the Ni2+-sensitive beating rate and downregulates the Ni2+-sensitive T-type Ca2+ channel current. Because the Ni2+-sensitive T-type Ca2+ channel current is largely composed of the Cav3.2-T-type Ca2+ channel, it is accordingly assumed that PKC activity plays a crucial role in the maintenance of the Cav3.2 channel. The expression of Cav3.2 mRNA was highly positively correlated with PKC activity. The expression of a transcription factor Nkx2.5 mRNA, possibly corresponding to the Cav3.2 channel gene, was decreased by an inhibition of PKCβII. These results suggest that PKC activation, presumably by PKCβII, is responsible for the upregulation of CaV3.2 T-type Ca2+ channel expression that interacts with a car-diac-specific transcription factor, Nkx2.5, in neonatal cardiomyocytes.
  • Masaki Morishima; Katsushige Ono
    Heart and vessels 36 10 1597 - 1606 2021年10月 [査読有り]
     
    We tested the hypothesis that angiotensin II (Ang II)-induced cardiovascular complications are distinguished from what catecholamine-induced by their serum circulating biomarkers in rats. Infusion of Ang II (1.68 mg/kg/day) significantly increased systolic and diastolic blood pressure assessed at week one or later, accompanied by an increase of heart/body weight ratio. Noradrenaline infusion (5.40 mg/kg/day) produced a similar degree of hypertension, but did not increase heart weight. Ang II-, but not noradrenaline-induced hypertension was associated with a drastic upregulation of serum microRNA-30d (miR-30d) by hundreds of times, accompanied by an increase of miR-30d levels in the atrium but not in the ventricle. Ang II, but not noradrenaline, significantly increased mRNA of brain natriuretic peptide (BNP) in the atrium. Studies using rat neonatal cardiomyocytes in vitro demonstrated that BNP caused an increase of miR-30d when applied for 6 h or longer in the culture medium. In vitro application of Ang II increased the cell size, although BNP and miR-30d were unable to mimic the effect of Ang II. We conclude that serum circulating microRNA-30d is a sensitive biomarker for Ang II-induced cardiovascular complications. It is also postulated that Ang II-induced cardiomyocyte hypertrophy could be independent of miR-30d/BNP signaling pathways.
  • Masaki Morishima; Takafumi Fujita; Satoshi Osagawa; Hiroshi Kubota; Katsushige Ono
    Membranes 11 7 470 - 470 2021年06月 [査読有り]
     
    Brain-derived neurotrophic factor (BDNF) has recently been recognized as a cardiovascular regulator particularly in the diseased condition, including coronary artery disease, heart failure, cardiomyopathy, and hypertension. Here, we investigate the role of BDNF on the T-type Ca2+ channel, Cav3.1 and Cav3.2, in rat neonatal cardiomyocytes exposed to normoxia (21% O2) and acute hypoxia (1% O2) in vitro for up to 3 h. The exposure of cardiomyocytes to hypoxia (1 h, 3 h) caused a significant upregulation of the mRNAs for hypoxia-inducible factor 1α (Hif1α), Cav3.1, Cav3.2 and Bdnf, but not tropomyosin-related kinase receptor B (TrkB). The upregulation of Cav3.1 and Cav3.2 caused by hypoxia was completely halted by small interfering RNA (siRNA) targeting Hif1a (Hif1a-siRNA) or Bdnf (Bdnf-siRNA). Immunocytochemical staining data revealed a distinct upregulation of Cav3.1- and Cav3.2-proteins caused by hypoxia in cardiomyocytes, which was markedly suppressed by Bdnf-siRNA. These results unveiled a novel regulatory action of BDNF on the T-type Ca2+ channels expression through the HIF-1α-dependent pathway in cardiomyocytes.
  • Pu Wang; Mengyan Wei; Xiufang Zhu; Yangong Liu; Kenshi Yoshimura; Mingqi Zheng; Gang Liu; Shinichiro Kume; Masaki Morishima; Tatsuki Kurokawa; Katsushige Ono
    Scientific reports 11 1 11273 - 11273 2021年05月 [査読有り]
     
    Nitric oxide (NO) is produced from endothelial cells and cardiomyocytes composing the myocardium and benefits cardiac function through both vascular-dependent and-independent effects. This study was purposed to investigate the possible adverse effect of NO focusing on the voltage-gated Na+ channel in cardiomyocytes. We carried out patch-clamp experiments on rat neonatal cardiomyocytes demonstrating that NOC-18, an NO donor, significantly reduced Na+ channel current in a dose-dependent manner by a long-term application for 24 h, accompanied by a reduction of Nav1.5-mRNA and the protein, and an increase of a transcription factor forkhead box protein O1 (FOXO1) in the nucleus. The effect of NOC-18 on the Na+ channel was blocked by an inhibitor of thiol oxidation N-ethylmaleimide, a disulfide reducing agent disulfide 1,4-Dithioerythritol, or a FOXO1 activator paclitaxel, suggesting that NO is a negative regulator of the voltage-gated Na+ channel through thiols in regulatory protein(s) for the channel transcription.
  • Ryusuke Suzuki; Masaki Morishima; Chisato Nakada; Shinji Miyamoto; Katsushige Ono
    Heart and vessels 36 4 577 - 588 2021年04月 [査読有り]
     
    This investigation was aimed to identify gene profiles in human atrial myocardium in response to chronic mechanical stretch. Right atrial appendages from 21 patients were divided into 2 groups based on the size of right atrial volume. The microarray DATA analyses differentially identified 335 genes (> 2.0-fold, corrected P < 0.05) including "functionally unknown genes". This study identified 26 up-regulated genes (natriuretic peptide B, G protein subunit gamma 13, thyroid stimulating hormone beta, etc.) and 23 down-regulated genes (oligodendrocyte transcription factor 1, carbonic anhydrase 12, etc.), which could be responsible for chronic stretch-mediated structural remodeling in the atrium.
  • Masaki Morishima; Shintaro Tahara; Yan Wang; Katsushige Ono
    Membranes 11 4 234  2021年03月 [査読有り]
     
    Oxytocin (OT) and its receptor (OTR) are expressed in the heart and are involved in the physiological cardiovascular functional system. Although it is known that OT/OTR signaling is cardioprotective by reducing the inflammatory response and improving cardiovascular function, the role of OT in the cardiac electrical excitation modulation has not been clarified. This study investigates the molecular mechanism of the action of OT on cardiomyocyte membrane excitation focusing on the L-type Ca2+ channel. Our methodology uses molecular biological methods and a patch-clamp technique on rat cardiomyocytes with OT, combined with several signal inhibitors and/or activators. Our results show that long-term treatment of OT significantly decreases the expression of Cav1.2 mRNA, and reduces the L-type Ca2+ channel current (ICa.L) in cardiomyocytes. OT downregulates the phosphorylated component of a transcription factor adenosine-3',5'-cyclic monophosphate (cAMP) response element binding protein (CREB), whose action is blocked by OTR antagonist and pertussis toxin, a specific inhibitor of the inhibitory GTP-binding regulators of adenylate cyclase, Gi. On the other hand, the upregulation of Cav1.2 mRNA expression by isoproterenol is halted by OT. Furthermore, inhibition of phospholipase C (PLC) was without effect on the OT action to downregulate Cav1.2 mRNA-which suggests a signal pathway of Gi/protein kinase A (PKA)/CREB mediated by OT/OTR. These findings indicate novel signaling pathways of OT contributing to a downregulation of the Cav1.2-L-type Ca2+ channel in cardiomyocytes.
  • Yan Wang; Masaki Morishima; Dan Li; Naohiko Takahashi; Tetsunori Saikawa; Stanley Nattel; Katsushige Ono
    Circulation journal : official journal of the Japanese Circulation Society 84 11 1931 - 1940 2020年10月 [査読有り]
     
    BACKGROUND: The association between binge alcohol ingestion and atrial fibrillation (AF), often termed "holiday heart syndrome", has long been recognized. However, the underlying cellular and molecular mechanisms are unknown.Methods and Results:An experimental model of binge alcohol-induced AF was developed to elucidate the mechanisms linking acute ethanol exposure to changes in ion channel transcription and AF susceptibility. AF-susceptibility during transesophageal electrical stimulation was enhanced 8 h after, but not immediately or 24 h after, acute alcohol intake. T-type calcium channel (TCC) blockade and calcineurin inhibition diminished the AF-promoting effect of ethanol. Long-term (8-24 h) exposure to ethanol augmented TCC isoform-expression (Cav3.1 and Cav3.2) and currents in cardiomyocytes, accompanied by upregulation of the transcription factors, Csx/Nkx2.5 and nuclear factor of activated T-cells (NFAT), in the nucleus, and of phospho-glycogen synthesis kinase 3β (GSK3β) in the cytosol. Inhibition of protein kinase C (PKC) during the 7- to 8-h period following ethanol exposure attenuated susceptibility to AF, whereas acute exposure did not. GSK3β inhibition itself upregulated TCC expression and increased AF susceptibility. CONCLUSIONS: The present study results suggest a crucial role for TCC upregulation in the AF substrate following binge alcohol-drinking, resulting from ethanol-induced PKC-activation that hyperphosphorylates GSK3β to cause enhanced calcineurin-NFAT-Csx/Nkx2.5 signaling. These observations elucidate for the first time the potential mechanisms underlying the clinically well-recognized, but mechanistically enigmatic, "holiday heart syndrome".
  • Toru Shimaoka; Yan Wang; Masaki Morishima; Shinji Miyamoto; Katsushige Ono
    Circulation journal : official journal of the Japanese Circulation Society 84 8 1244 - 1253 2020年07月 [査読有り]
     
    BACKGROUND: Mechanisms for QT interval prolongation and cardiac arrhythmogenesis in hypomagnesemia are poorly understood. This study investigated the potential molecular mechanism for QT prolongation caused by magnesium (Mg) deficiency in rats by using the patch clamp technique and molecular biology.Methods and Results:Male Wistar rats were fed an Mg-free diet or a normal diet for up to 12 weeks. There was QT prolongation in the ECG of Mg-deficient rats, and cardiomyocytes from these rats showed prolongation of action potential duration. Electrophysiological studies showed that inward-rectifying K+current (IK1) and transient outward K+current (Ito) were decreased in Mg-deficient cardiomyocytes, and these findings were consistent with the downregulation of mRNA, as well as protein levels of Kir2.1 and Kv4.2. In Mg-deficient cardiomyocytes, transcription factors, GATA4 and NFAT, were upregulated, whereas CREB was downregulated. In contrast to Mg deficiency, cellular Mg2+overload in cultured cardiomyocytes resulted in the upregulation of Kir2.1 and Kv4.2, which was accompanied by the downregulation of GATA4 and NFATc4, and the upregulation of CREB. Activation of NFAT and inhibition of CREB reduced Kv4.2-Ito, whereas Kir2.1-IK1was reduced by CREB inhibition but not by NFTA activation. CONCLUSIONS: Intracellular Mg deficiency downregulates IK1and Itoin cardiomyocytes, and this is mediated by the transcription factors, NFAT and CREB. These results provide a novel mechanism for the long-term QT interval prolongation in hypomagnesemia.
  • Kimiko Masuda; Hiroki Takanari; Masaki Morishima; FangFang Ma; Yan Wang; Naohiko Takahashi; Katsushige Ono
    The journal of physiological sciences : JPS 68 6 759 - 767 2018年11月 [査読有り]
     
    Men have shorter rate-corrected QT intervals (QTc) than women, especially at the period of adolescence or later. The aim of this study was to elucidate the long-term effects of testosterone on cardiac excitability parameters including electrocardiogram (ECG) and potassium channel current. Testosterone shortened QT intervals in ECG in castrated male rats, not immediately after, but on day 2 or later. Expression of Kv7.1 (KCNQ1) mRNA was significantly upregulated by testosterone in cardiomyocytes of male and female rats. Short-term application of testosterone was without effect on delayed rectifier potassium channel current (IKs), whereas IKs was significantly increased in cardiomyocytes treated with dihydrotestosterone for 24 h, which was mimicked by isoproterenol (24 h). Gene-selective inhibitors of a transcription factor SP1, mithramycin, abolished the effects of testosterone on Kv7.1. Testosterone increases Kv7.1-IKs possibly through a pathway related to a transcription factor SP1, suggesting a genomic effect of testosterone as an active factor for cardiac excitability.
  • Masaki Morishima; Kazuki Horikawa; Makoto Funaki
    PloS one 13 8 e0201891  2018年 [査読有り]
     
    RATIONALE: Diabetes causes cardiac dysfunction, and understanding of its mechanism is still incomplete. One reason could be limitations in modeling disease conditions by current in vitro cardiomyocyte culture. Emerging evidence suggests that the mechanical properties of the microenvironment affect cardiomyocyte function. Nevertheless, the impact of high glucose on cardiomyocytes cultured on substrates whose stiffness matches that of the heart (approximately 15 kPa) is untested. OBJECTIVE: To test the hypothesis that cardiomyocytes cultured in microenvironments that mimic the mechanical properties of those for cardiomyocytes in vivo may reproduce the pathophysiology characteristics of diabetic cardiomyocytes ex vivo, such as the morphological appearance, ROS accumulation, mitochondrial dysfunction, apoptosis and insulin-stimulated glucose uptake. METHODS AND RESULTS: Isolated neonatal rat cardiomyocytes were seeded on 15 kPa polyacrylamide (PAA) gels, whose stiffness mimics that of heart tissues, or on glass coverslips, which represent conventional culture devices but are unphysiologically stiff. Cells were then cultured at 5 mM glucose, corresponding to the normal blood glucose level, or at high glucose levels (10 to 25 mM). Cytoskeletal disorganization, ROS accumulation, attenuated mitochondrial membrane potential and attenuated ATP level caused by high glucose and their reversal by a ROS scavenger were prominent in cells on gels, but not in cells on coverslips. The lack of response to ROS scavenging could be attributable to enhanced apoptosis in cells on glass, shown by enhanced DNA fragmentation and higher caspase 3/7 activity in cells on glass coverslips. High-glucose treatment also downregulated GLUT4 expression and attenuated insulin-stimulated glucose uptake only in cells on 15 kPa gels. CONCLUSION: Our data suggest that a mechanically compliant microenvironment increases the susceptibility of primary cardiomyocytes to elevated glucose levels, which enables these cells to serve as an innovative model for diabetic heart research.
  • Fangfang Ma; Hiroki Takanari; Kimiko Masuda; Masaki Morishima; Katsushige Ono
    Heart and vessels 31 7 1176 - 84 2016年07月 [査読有り]
     
    Bepridil is an effective antiarrhythmic drug on supraventricular and ventricular arrhythmias, and inhibitor of calmodulin. Recent investigations have been elucidating that bepridil exerts antiarrhythmic effects through its acute and chronic application for patients. The aim of this study was to identify the efficacy and the potential mechanism of bepridil on the inward-rectifier potassium channel in neonatal rat cardiomyocytes in acute- and long-term conditions. Bepridil inhibited inward-rectifier potassium current (I K1) as a short-term effect with IC50 of 17 μM. Bepridil also reduced I K1 of neonatal cardiomyocytes when applied for 24 h in the culture medium with IC50 of 2.7 μM. Both a calmodulin inhibitor (W-7) and an inhibitor of calmodulin-kinase II (KN93) reduced I K1 when applied for 24 h as a long-term effect in the same fashion, suggesting that the long-term application of bepridil inhibits I K1 more potently than that of the short-term application through the inhibition of calmodulin kinase II pathway in cardiomyocytes.
  • Masaki Morishima; Eriko Iwata; Chisato Nakada; Yoshiyuki Tsukamoto; Hiroki Takanari; Shinji Miyamoto; Masatsugu Moriyama; Katsushige Ono
    Circulation journal : official journal of the Japanese Circulation Society 80 6 1346 - 55 2016年05月 [査読有り]
     
    BACKGROUND: Atrial fibrillation (AF) begets AF in part due to atrial remodeling, the molecular mechanisms of which have not been completely elucidated. This study was conducted to identify microRNA(s) responsible for electrical remodeling in AF. METHODS AND RESULTS: The expression profiles of 1205 microRNAs, in cardiomyocytes from patients with persistent AF and from age-, gender-, and cardiac function-matched control patients with normal sinus rhythm, were examined by use of a microRNA microarray platform. Thirty-nine microRNAs differentially expressed in AF patients' atria were identified, including miR-30d, as a candidate responsible for ion channel remodeling by in silico analysis. MiR-30d was significantly upregulated in cardiomyocytes from AF patients, whereas the mRNA and protein levels ofCACNA1C/Cav1.2 andKCNJ3/Kir3.1, postulated targets of miR-30d, were markedly reduced.KCNJ3/Kir3.1 expression was downregulated by transfection of the miR-30 precursor, concomitant with a reduction of the acetylcholine-sensitive inward-rectifier K(+)current (IK.ACh).KCNJ3/Kir3.1 (but notCACNA1C/Cav1.2) expression was enhanced by the knockdown of miR-30d. The Ca(2+)ionophore, A23187, induced a dose-dependent upregulation of miR-30d, followed by the suppression ofKCNJ3mRNA expression. Blockade of protein kinase C signaling blunted the [Ca(2+)]i-dependent downregulation of Kir3.1 via miR-30d. CONCLUSIONS: The downward remodeling ofIK.AChis attributed, at least in part, to deranged Ca(2+)handling, leading to the upregulation of miR-30d in human AF, revealing a novel post-transcriptional regulation ofIK.ACh. (Circ J 2016; 80: 1346-1355).
  • Toru Shimaoka; Yan Wang; Masaki Morishima; Shinji Miyamoto; Katsushige Ono
    Pathophysiology : the official journal of the International Society for Pathophysiology 22 2 87 - 93 2015年06月 [査読有り]
     
    The present study was designed to investigate the effect of magnesium (Mg) depletion on the expression of voltage-gated calcium (Ca(2+)) channels and Ca(2+) currents in the heart and thereby on hypomagnesemic arrhythmogenesis in adult male rats. Male Wistar rats were fed an Mg-free diet or a normal diet for up to 16 weeks. Serum Mg concentrations were significantly reduced at week 4 or later with an Mg-free diet, which experimentally represents hypomagnesemia. Myocardial Mg contents were also reduced at week 16 accompanied by myocardial hypertrophy. Telemetric ECG recordings revealed a long-term changes of ECG parameters in hypomagnesemic rats; RR shortening, QT prolongation and appreciable PR prolongation. At the same time, hypomagnesemic rats demonstrate various bradycardiac arrhythmias including ventricular premature beats, atrioventricular blocks and sinus arrest, which were never recoded in rats fed by a normal diet. Electrophysiological studies elucidated that the L-type Ca(2+) channel current was decreased in Mg-deficient cardiomyocytes, and these findings were consistent with down-regulation of CaV1.2-mRNA but not in levels of CaV1.3, CaV3.1 or CaV3.2. These findings provide novel insights into hypomagnesemic electrophysiological disorders in the heart, and should be considered when assessing the design of effective antiarrhythmic treatments in patients with hypomagnesemia.
  • Takamasa Ohnishi; Fumiko Hisaoka; Masaki Morishima; Akira Takahashi; Nagakatsu Harada; Kazuaki Mawatari; Hidekazu Arai; Emiko Yoshioka; Satomi Toda; Izumi Keisuke; Yutaka Nakaya
    Journal of toxicologic pathology 27 1 51 - 6 2014年04月 [査読有り]
     
    Studies that investigate the underlying mechanisms of disease and treatment options typically require the use of a suitable animal model. Few suitable animal models exist for left atrial thrombosis. Here, we demonstrated that the Spontaneously-Running-Tokushima-Shikoku (SPORTS) rat - a Wistar strain known for its running ability-is predisposed to the development of thrombi in the left atrium. We investigated the incidence of left atrial thrombosis in male (n = 16) and female (n = 17) SPORTS rats and observed organized atrial thrombosis in 57% and 38% of males and female rats, respectively. In the male rats, systolic blood pressures and heart rates were significantly higher in SPORTS rats than in control Wistar rats. We could not find any evidence of arrhythmias, such as atrial fibrillation, during electrocardiographic examination of SPORTS rats. We believe that the SPORTS rat could serve as a new research model for left atrial thrombosis; further, it may be suitable for research investigating the development of new antithrombotic approaches for the control of atrial thrombosis or familial thrombophilia in humans.
  • Kazuaki Mawatari; Emiko Yoshioka; Satomi Toda; Sonoko Yasui; Hiroko Furukawa; Takaaki Shimohata; Takamasa Ohnishi; Masaki Morishima; Nagakatsu Harada; Akira Takahashi; Hiroshi Sakaue; Yutaka Nakaya
    Circulation journal : official journal of the Japanese Circulation Society 78 8 1980 - 8 2014年 [査読有り]
     
    BACKGROUND: Left atrial (LA) thrombosis is an important cause of systemic embolization. The SPORTS rat model of LA thrombi (Spontaneously-Running Tokushima-Shikoku), which have a unique characteristic of high voluntary wheel running, was previously established. The aim of the present study was to investigate how SPORTS rats develop LA thrombi. METHODS AND RESULTS: Nitric oxide (NO) produced from cardiovascular endothelial cells plays an important protective role in the local regulation of blood flow, vascular tone, and platelet aggregation. No evidence of atrial fibrillation or hypercoagulability in SPORTS rats regardless of age was found; however, SPORTS rats demonstrated endothelial dysfunction and a decrease of NO production from a young age. In addition, endothelial NO synthase activity was significantly decreased in the LA and thoracic aorta endothelia of SPORTS rats. While voluntary wheel running was able to intermittently increase NO levels, running did not statistically decrease the incidence of LA thrombi at autopsy. However, L-arginine treatment significantly increased NO production and provided protection from the development of LA thrombi in SPORTS rats. CONCLUSIONS: They present study results indicate that NO has an important role in the development of LA thrombus, and endothelia pathways could provide new targets of therapy to prevent LA thrombosis.
  • Masaki Morishima; Shintaro Tahara; Yan Wang; Toshihiko Kaku; Katsushige Ono
    Journal of Arrhythmia 26 2 111 - 118 2010年 [査読有り]
     
    Background: The neurohypophyseal hormones oxytocin (OT) and [Arg8]-vasopressin (AVP) have recently been implicated in cardiac function. This study was designed to investigate actions of OT and AVP on regulation of the voltage-gated Ca2+ channel in cardiomyocytes. Methods and Results: Cultured neonatal rat cardiomyocytes were stimulated with OT or AVP (10~8 M to 10~6 M) for 24-72 h, followed by real-time PCR and patch clamp studies. Although OT did not exert any modulatory effect on L-type Ca2+ channel current, as a short-term effect, stimulation of cardiomyocytes with OT but not AVP decreased the expression of CaV1.2 mRNA with a reduced L-type Ca2+ channel current. A transcription factor CREB mRNA expression was down-regulated by OT treatment, although T-type Ca2+ channels (CaV3.1, CaV3.2) were unaffected by OT or AVP. Conclusion: OT but not AVP down-regulates L-type Ca2+ channel expression through the inhibition of CREB transcriptional, suggesting a novel mechanism of OT action in the cardiac electrophysiology. © 2010, Japanese Heart Rhythm Society. All rights reserved.
  • Atsushi Hattori; Kazuaki Mawatari; Satomi Tsuzuki; Emiko Yoshioka; Satomi Toda; Masaki Yoshida; Sonoko Yasui; Hiroko Furukawa; Masaki Morishima; Katsushige Ono; Takamasa Ohnishi; Masayuki Nakano; Nagakatsu Harada; Akira Takahashi; Yutaka Nakaya
    Obesity (Silver Spring, Md.) 18 1 48 - 54 2010年01月 [査読有り]
     
    We established a new animal model called SPORTS (Spontaneously-Running Tokushima-Shikoku) rats, which show high-epinephrine (Epi) levels. Recent reports show that Epi activates adenosine monophosphate (AMP)-activated protein kinase (AMPK) in adipocytes. Acetyl-CoA carboxylase (ACC) is the rate-limiting enzyme in fatty acid synthesis, and the enzymatic activity is suppressed when its Ser-79 is phosphorylated by AMPK. The aim of this study was to investigate the in vivo effect of Epi on ACC and abdominal visceral fat accumulation. We divided both 6-week male control and SPORTS rats into two groups, which were fed either normal diet or high fat and sucrose (HFS) diet for 16 weeks. At the end of diet treatment, retroperitoneal fat was collected for western blotting and histological analysis. Food intake was not different among the groups, but SPORTS rats showed significantly lower weight gain than control rats in both diet groups. After 10 weeks of diet treatment, glucose tolerance tests (GTTs) revealed that SPORTS rats had increased insulin sensitivity. Furthermore, SPORTS rats had lower quantities of both abdominal fat and plasma triglyceride (TG). In abdominal fat, elevated ACC Ser-79 phosphorylation was observed in SPORTS rats and suppressed by an antagonist of beta-adrenergic receptor (AR), propranolol, or an inhibitor of AMPK, Compound C. From these results, high level of Epi induced ACC phosphorylation mediated through beta-AR and AMPK signaling pathways in abdominal visceral fat of SPORTS rats, which may contribute to reduce abdominal visceral fat accumulation and increase insulin sensitivity. Our results suggest that beta-AR-regulated ACC activity would be a target for treating lifestyle-related diseases, such as obesity.
  • L. Kang; M. Q. Zheng; M. Morishima; Y. Wang; T. Kaku; K. Ono
    British Journal of Pharmacology 157 3 404 - 414 2009年06月 [査読有り]
     
    Background and purpose: Bepridil is an anti-arrhythmic agent with anti-electrical remodelling effects that target many cardiac ion channels, including the voltage-gated Na + channel. However, long-term effects of bepridil on the Na - channel remain unclear. We explored the long-term effect of bepridil on the Na + channel in isolated neonatal rat cardiomyocytes and in a heterologous expression system of human Na v1.5 channel. Experimental approach: Na + currents were recorded by whole-cell voltage-clamp technique. Na + channel message and protein were evaluated by real-time RT-PCR and Western blot analysis. Key results: Treatment of cardiomyocytes with 10 μmol-L -1 bepridil for 24 h augmented Na + channel current (/ Na) in a dose- and time-dependent manner. This long-term effect of bepridil was mimicked or masked by application of W-7, a calmodulin inhibitor, but not KN93 [2-[N-(2- hydroxyethyl)-N-(4-methoxy benzenesulphonyl)]-amino-N-(4-chlorocinnamyl)N- methylbenzylamine], a Ca 2+/calmodulin-dependent kinase inhibitor. During inhibition of protein synthesis by cycloheximide, the / Na increase due to bepridil was larger than the increase without cycloheximide. Bepridil and W-7 significantly slowed the time course of Na v1.5 protein degradation in neonatal cardiomyocytes, although the mRNA levels of Nav1.5 were not modified. Bepridil and W-7 did not increase / Na any further in the presence of the proteasome inhibitor MGI32 [N[(phenylmethoxy) carbonyl]-L-leucyl-N-[(1S)-1-formyl-3-methylbutyl]-L-leucinamide]. Bepridil, W-7 and MC132 but not KN93 significantly decreased 20S proteasome activity in a concentration-dependent manner. Conclusions and implications: We conclude that long-term exposure of cardiomyocytes to bepridil at therapeutic concentrations inhibits calmodulin action, which decreased degradation of the Na v1.5 a-subunit, which in turn increased Na + current. © 2009 The British Pharmacological Society All rights reserved.
  • Masaki Morishima; Yan Wang; Yuko Akiyoshi; Shinji Miyamoto; Katsushige Ono
    European journal of pharmacology 609 1-3 105 - 12 2009年05月 [査読有り]
     
    Recently, it has been revealed that angiotensin II type 1 receptor (AT(1)) antagonists act as antiarrhythmic agents and that the T-type Ca2+ channel plays an important role in arrhythmia. However, it remains unclear how the T-type Ca2+ channel expression system is involved in angiotensin II-mediated arrhythmogenesis in cardiomyocytes. In this study, we investigated the effect of telmisartan, an AT(1) receptor antagonist, on transcriptional regulation of T-type Ca2+ channel isoform (Ca(v)3.1 and Ca(v)3.2) expression and cardiac contractility using rat neonatal cardiomyocytes. Cultured cardiomyocytes were stimulated with telmisartan and/or angiotensin II for 24 h. T-type Ca2+ currents (I(Ca.T)) were then measured with the patch clamp technique, while Ca(v)3.1 and Ca(v)3.2 mRNA expression were assessed by real-time PCR. Expression of Ca(v)3.1 and Ca(v)3.2 mRNA as well as I(Ca.T) current density in cardiomyocytes increased significantly after long-term application of angiotensin II (24 h), which was accompanied by extracellular signal-regulated kinase (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK) phosphorylation. In contrast, telmisartan decreased Ca(v)3.1 and Ca(v)3.2 mRNA expression as well as I(Ca.T) in a dose-dependent manner in the absence of angiotensin II. In addition, the basal phosphorylation level of p38MAPK but not ERK1/2 was decreased by telmisartan in the absence of angiotensin II. Valsartan, an AT(1) receptor antagonist, did not mimic the action of telmisartan, while the action of telmisartan was completely blocked by valsartan. These results indicate that telmisartan attenuates T-type Ca2+ channel expression likely through p38MAPK activity in an agonist-independent manner, which suggests a novel pharmacological action of telmisartan.
  • Farzana Marni; Yan Wang; Masaki Morishima; Toru Shimaoka; Tomoko Uchino; Mingqi Zheng; Toshihiko Kaku; Katsushige Ono
    Endocrinology 150 2 879 - 88 2009年02月 [査読有り]
     
    T-type Ca(2+) channel current (I(Ca,T)) plays an important role for spontaneous pacemaker activity and is involved in the progression of structural heart diseases. Estrogens are of importance for the regulation of growth and differentiation and function in a wide array of target tissues, including those in the cardiovascular system. The aim of this study was to elucidate the short-term and long-term effects of 17beta-estradiol (E(2)) on I(Ca,T) in cardiomyocytes. We employed in vivo and in vitro techniques to clarify E(2)-mediated modulation of heart rate (HR) in ovariectomized rats and I(Ca,T) in cardiomyocytes. Ovariectomy increased HR and E(2) supplement reduced HR in ovariectomized rats. Slowing of E(2)-induced HR was consistent with the deceleration of automaticity in E(2)-treated neonatal cardiomyocytes. Short-term application of E(2) did not have significant effects on I(Ca,T), whereas in cardiomyocytes treated with 10 nm E(2) for 24 h, estrogen receptor-independent down-regulation of peak I(Ca,T) and declination of Ca(V)3.2 mRNA were observed. Expression of a cardiac-specific transcription factor Csx/Nkx2.5 was also suppressed by E(2) treatment for 24 h. On the other hand, expression of Ca(V)3.1 mRNA was unaltered by E(2) treatment in this study. An ERK-1/2, 5 inhibitor, PD-98059, abolished the effects of E(2) on I(Ca,T) and Ca(V)3.2 mRNA as well as Csx/Nkx2.5 mRNA. These findings indicate that E(2) decreases Ca(V)3.2 I(Ca,T) through activation of ERK-1/2, 5, which is mediated by the suppression of Csx/Nkx2.5-dependent transcription, suggesting a genomic effect of E(2) as a negative chronotropic factor in the heart.
  • Yan Wang; Masaki Morishima; Mingqi Zheng; Tomoko Uchino; Kazuaki Mannen; Akira Takahashi; Yutaka Nakaya; Issei Komuro; Katsushige Ono
    Journal of molecular and cellular cardiology 42 6 1045 - 53 2007年06月 [査読有り]
     
    The cardiac transcription factors Csx/Nkx2.5 and GATA4 play important roles in vertebrate heart development. Although mutations of Csx/Nkx2.5 or GATA4 are associated with various congenital heart diseases, their mechanism of action on cardiomyocyte function is not completely elucidated. In this study, we therefore investigated the actions of these transcription factors on the electrophysiological features and expression of ion channels in cardiomyocytes. Genes for transcription factors Csx/Nkx2.5 and GATA4 were transfected into rat neonatal cardiomyocytes by adenoviral infection. Action potentials, L-, T-type Ca(2+) channels and hyperpolarization-activated cation current (I(h)) of rat neonatal myocytes were recorded by patch clamp technique after adenoviral infection. Expression of ion channels was confirmed by real-time PCR. In Csx/Nkx2.5 overexpression myocytes, the spontaneous beating rate was markedly increased with an up-regulation of the Ca(v)3.2 T-type Ca(2+) channel, while in GATA4 overexpression myocytes, the T-type Ca(2+) channel was unchanged. On the other hand, the L-type Ca(2+) channel was down-regulated by both Csx/Nkx2.5 and GATA4 overexpression; the level of Ca(v)1.3 mRNA was dramatically decreased by Csx/Nkx2.5 overexpression. These results indicate that Csx/Nkx2.5 and GATA4 play important roles on the generation of pacemaker potentials modulating voltage-dependent Ca(2+) channels in the neonatal cardiomyocyte.
  • Nagakatsu Harada; Akiko Kusuyama; Masaki Morishima; Kazuko Okada; Akira Takahashi; Yutaka Nakaya
    Metabolism: clinical and experimental 56 4 517 - 22 2007年04月 [査読有り]
     
    Bacterial endotoxin/lipopolysaccharide (LPS)-induced cachexia is characterized by weight loss, anorexia, and a disturbance in lipid metabolism, namely, hypertriacylglycerolemia. The aim of this study in rats with acute endotoxicity induced by an injection of LPS was to investigate whether bezafibrate, a ligand for peroxisome proliferator-activated receptor alpha and a lipoprotein lipase (LPL) activator, improved cachectic conditions, including impaired lipid metabolism. Short-term administration of LPS in the rats resulted in impairment of triacylglycerol clearance in plasma after the intake of fresh cream. In addition, LPS increased whole-body energy expenditure, reduced fasting body weight and caused anorexia in the rats. Bezafibrate treatment resulted in significant improvements in LPS-induced dyslipidemia and anorexia, but had no effect on energy expenditure, respiratory quotient, or fasting body weight in the endotoxic rats. Administration of LPS was also associated with a decrease in the level of messenger RNA (mRNA) expression for LPL in white adipose tissue and skeletal muscle and an increase in the mRNA levels for uncoupling protein 3 in skeletal muscle. Bezafibrate treatment reversed the decline in LPL mRNA levels in white adipose tissue but not in the skeletal muscle tissue of the rats. The enhanced uncoupling protein 3 mRNA level in the endotoxic rats was not affected by bezafibrate treatment. Plasma concentration of leptin was increased by short-term LPS treatment. Bezafibrate decreased the level of plasma leptin significantly without affecting the level of leptin mRNA expression. These results suggest that bezafibrate may be an effective drug not only for impaired triacylglycerol metabolism, but also for anorexia in cachectic states induced by bacterial infections.
  • Masaki Morishima; Nagakatsu Harada; Sayuri Hara; Atsuko Sano; Hiromasa Seno; Akira Takahashi; Yusuke Morita; Yutaka Nakaya
    Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 31 12 2627 - 38 2006年12月 [査読有り]
     
    An understanding of neurological mechanisms for wheel running by rodents, especially with high exercise activity, would be applicable to a strategy for promotion of exercise motivation in humans. One of several brain regions that are candidates for the regulation of physical exercise is the hippocampus. Here we examined the running activity of Spontaneously-Running-Tokushima-Shikoku (SPORTS) rat, a new animal model for high levels of wheel-running activity, and its relation with the hippocampal norepinephrine (NE) system including the levels of NE, adrenergic receptors, and degradation enzymes for monoamines. In the hippocampus of SPORTS rats, the level of NE in extracellular fluid was augmented, whereas the level in the homogenate of the whole tissue was decreased even for sedentary conditions. Elevated extracellular NE caused downregulation of alpha(2)-adrenergic receptors in the hippocampus of SPORTS rats. Local administration of alpha(2)-adrenergic receptor antagonist yohimbine, but not of alpha(2)-agonist clonidine, into the hippocampus suppressed high running activity in SPORTS rats. The protein expression and the activity levels of monoamine oxidase A (MAOA), a critical enzyme for the degradation of NE, were decreased in the hippocampus of SPORTS rats to increase extracellular NE level. Thus, inhibition of oxidase activity in normal Wistar rats markedly increased wheel-running activity. These results indicate that decreased MAOA activity, elevation of extracellular NE, and alpha(2)-adrenergic receptors in the hippocampus determine the neural basis of the psychological regulation of exercise behavior in SPORTS rats.
  • Sachiko Chikahisa; Hiroyoshi Sei; Masaki Morishima; Atsuko Sano; Kazuyoshi Kitaoka; Yutaka Nakaya; Yusuke Morita
    Behavioural brain research 169 2 312 - 9 2006年05月 [査読有り]
     
    Music has been suggested to have a beneficial effect on various types of performance in humans. However, the physiological and molecular mechanism of this effect remains unclear. We examined the effect of music exposure during the perinatal period on learning behavior in adult mice, and measured the levels of brain-derived neurotrophic factor (BDNF) and its receptor, tyrosine kinase receptor B (TrkB), which play critical roles in synaptic plasticity. In addition, we measured the levels of 3-phosphoinositide-dependent protein kinase-1 (PDK1) and mitogen-activated protein kinase (MAPK), downstream targets of two main pathways in BDNF/TrkB signaling. Music-exposed mice completed a maze learning task with fewer errors than the white noise-exposed mice and had lower levels of BDNF and higher levels of TrkB and PDK1 in the cortex. MAPK levels were unchanged. Furthermore, TrkB and PDK1 protein levels in the cortex showed a significant negative correlation with the number of errors on the maze. These results suggest that perinatal exposure of mice to music has an influence on BDNF/TrkB signaling and its intracellular signaling pathway targets, including PDK1, and thus may induce improved learning and memory functions.
  • Yutaka Nakaya; Masaki Morishima-Yamato; Kaori Ishida; Nagakatsu Harada; Masayuki Nakano
    Journal of Medical Investigation 52 SUPPL. 244  2005年11月 [査読有り]
     
    A stress-resistant rat model was introduced. SPORTS (Spontaneously-Running- Tokushima-Shikoku) rats showed significantly shorter time of immobility in the forced swim test compared to control Wister rats. Increase norepinephrine concentration secondary to decreased activity of monoamine oxidase A (MAOA) in hippocampus was observed in this model rats. This model rats are considered to be useful for studying the mechanism of psychological stress.
  • Masaki Morishima-Yamato; Fumiko Hisaoka; Sachiko Shinomiya; Nagakatsu Harada; Hideki Matoba; Akira Takahashi; Yutaka Nakaya
    Life Sciences 77 5 551 - 561 2005年06月 [査読有り]
     
    We generated an original Wistar line of rats that displayed increased levels of wheel running, which we named SPORTS (Spontaneously-Running-Tokushima- Shikoku). Male SPORTS rats ran voluntarily in a running wheel almost six times longer than male control Wistar rats, established without selection for their running activity. The running phenotype of female SPORTS rats was the same as female control Wistar rats. However, male offspring from the cross-mating between a female SPORTS rat and a male control rat also showed a similar level of hyper-running activity as the original SPORTS line. Compared to control rats, male SPORTS rats had lower levels of mean body weight, abdominal fat and plasma insulin after 4 weeks of running. It is likely that all these beneficial changes observed in the SPORTS rats reflected the increases in glucose disposal we observed in oral glucose tolerance tests carried out on the animals. We also found hyper-running caused a significant increase in skeletal muscle oxidative capacity, measured as the ratio of malate dehydrogenase to phosphofructokinase activity, an index of aerobic metabolism. These results indicate that the SPORTS rat may be a good animal model for determining the mechanisms responsible for up-regulation of running motivation, in addition to investigating changes in nutrient metabolism induced by high intensity exercise. © 2005 Elsevier Inc. All rights reserved.
  • Nagakatsu Harada; Chika Ninomiya; Yoshie Osako; Masaki Morishima; Kazuaki Mawatari; Akira Takahashi; Yutaka Nakaya
    Obesity research 12 7 1077 - 84 2004年07月 [査読有り]
     
    OBJECTIVE: To assess the effect of taurine supplementation on respiratory gas exchange, which might reflect the improved metabolism of glucose and/or lipid in the type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. RESEARCH METHODS AND PROCEDURES: Male OLETF rats (16 weeks of age) were randomly divided into two groups: unsupplemented group and taurine-supplemented (3% in drinking water) group. After 9 weeks of treatment, indirect calorimetry and insulin tolerance tests were conducted. The amounts of visceral fat pads, tissue glycogen, the blood concentrations of glucose, triacylglycerol, taurine, and electrolytes, and the level of hematocrit were compared between groups. A nondiabetic rat strain (Long-Evans Tokushima Otsuka) was used as the age-matched normal control. RESULTS: The indirect calorimetry showed that the treatment of OLETF rats with taurine could reduce a part of postprandial glucose oxidation possibly responsible for the increase of triacylglycerol synthesis in the body. Taurine supplementation also improved hyperglycemia and insulin resistance and increased muscle glycogen content in the OLETF rats. Supplementation with taurine increased the blood concentration of taurine and electrolyte and fluid volume, all of which were considered to be related to the improvement of metabolic disturbance in OLETF rats. DISCUSSION: Taurine supplementation may be an effective treatment for glucose intolerance and fat/lipid accumulation observed in type 2 diabetes associated with obesity. These metabolic changes might be ascribed, in part, to the alteration of circulating blood profiles, where the improved hyperglycemia and/or the blood accumulation of taurine itself would play roles.
  • Eiko Takishita; Akira Takahashi; Nagakatsu Harada; Masaki Yamato; Masaki Yamato; Yutaka Nakaya
    Journal of Cardiovascular Pharmacology 43 2 266 - 270 2004年02月 [査読有り]
     
    5-hydroxytryptamine (5-HT) is closely related to pathogenesis of angiopathy in type 2 diabetes. Acute and chronic effects of sarpogrelate hydrochloride (sarpogrelate), a 5-HT2 blocker, on glucose tolerance and insulin resistance were examined. Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes, were randomly assigned to 2 groups; those with 30 mg/kg BW/d sarpogrelate treatment of 4 weeks (HTB group) and without (control group). The glucose infusion rate was significantly increased in the HTB group compared with the control group. The blood glucose levels after oral glucose tolerance test and levels of plasma insulin and lipids were significantly lower in the HTB group than in the control group. To investigate mechanism of the improvement by sarpogrelate, acute effect of 5-HT and its blocking effect by sarpogrelate on blood levels of glucose were examined in 25-week-old Sprague-Dawley rats. Blood glucose levels were significantly increased by administration of 5-HT. This increase was reversed by pretreatment of sarpogrelate. A plasma adrenaline level also rose significantly by injection of the 5-HT and was prevented by pretreatment of sarpogrelate. These results indicate that sarpogrelate improves insulin resistance in type 2 diabetic rats.
  • Sachinobu Manabe; Ikuyo Kurroda; Kazuko Okada; Masaki Morishima; Miki Okamoto; Nagakatsu Harada; Akira Takahashi; Kentaro Sakai; Yutaka Nakaya
    Journal of nutritional science and vitaminology 49 6 375 - 80 2003年12月 [査読有り]
     
    Taurine is reported to increase contractility of skeletal muscle and cardiac myocyte, which can increase exercise performance. The present study aimed to clarify taurine's effect on chronic endurance exercise, especially accumulation of lactic acid (LA), a marker of fatigue and ability of aerobic exercise, and urinary secretion of 3-methylhistidine (3-MH), a marker of muscle breakdown in rats. After exercise blood levels of LA and urinary excretion of 3-MH were significantly increased and this increase was significantly less in those with chronic treatment of taurine. Taurine treatment also significantly decreased fat accumulation and blood levels of cholesterol and triglyceride, which might improve insulin resistance and utilization of fat and glucose. These results indicate taurine treatment is useful for reducing physical fatigue and muscle damage during exercise training in rats, presumably due to antioxidant property and improvement of muscle and cardiac functions by taurine.

講演・口頭発表等

  • Masaki Morishima
    第101回日本生理学会大会シンポジウム 2024年03月 シンポジウム・ワークショップパネル(公募)
  • 子どもの食事と発達との関係性  [招待講演]
    森島真幸
    1歳6か月健康診査等従事者研修会 2024年01月 公開講演,セミナー,チュートリアル,講習,講義等
  • Utilization of non-standard products and development of health promotion  [招待講演]
    Masaki Morishima
    Furikake: Healthy Savory Sprinkles 2023年11月 公開講演,セミナー,チュートリアル,講習,講義等
  • おいしさの「見える化」ー食品の官能検査ー
    令和5年後第67回農業実験実習講習会(近畿大学附属湯浅農場) 2023年07月 公開講演,セミナー,チュートリアル,講習,講義等
  • 人と地球の健康を目指した食環境整備  [招待講演]
    森島 真幸
    近畿大学x神戸大学SDGsフォーラム 「食の循環」~大阪湾を囲んだ二つの大学、初のアクション~ 2023年07月 シンポジウム・ワークショップパネル(指名)
  • The effects of omega-3 polyunsaturated fatty acids on cardiac rhythm and electrical excitability  [招待講演]
    Masaki Morishima
    第69回日本不整脈心電学会学術大会 心電学サミット 2023年07月 シンポジウム・ワークショップパネル(指名)
  • 「近大ふりかけ」で自然と健康になれる食環境の実現へ
    森島 真幸
    近畿大学農学部公開講座2023 2023年05月 公開講演,セミナー,チュートリアル,講習,講義等
  • 食生活と心機能 ー多価不飽和脂肪酸の栄養機能性ー  [招待講演]
    森島 真幸
    日本生理学会100回記念大会 2023年03月 口頭発表(招待・特別)
  • コロナ禍に負けない身体づくりと食環境整備  [招待講演]
    森島 真幸
    はりま産学交流会 2022年10月 公開講演,セミナー,チュートリアル,講習,講義等
  • 未利用食材の活用によるポストコロナ時代の食環境整備  [招待講演]
    森島 真幸
    近畿大学研究シーズ発表会 2022年09月 公開講演,セミナー,チュートリアル,講習,講義等

MISC

産業財産権

受賞

  • 2024年03月 第21回日本小児栄養研究会 優秀賞
     エイコサペンタエン酸(EPA)による栄養介入が心房細動の発症予防に及ぼす影響 
    受賞者: 堀井鴻佑、増田誠司、森島真幸
  • 2024年03月 第21回日本小児栄養研究会 最優秀賞
     健康な雌マウスへの妊娠前からのα-glucosylhesperidinの摂取が仔の情動的ストレスや免疫調節に及ぼす影響 
    受賞者: 鈴木巴乃;ZHU MOHAN;松永華奈;堀井鴻佑;森島真幸
  • 2023年08月 第32回日本病態生理学会大会 学部学生・修士課程大学院生セッション 優秀賞
     健康な雌性マウスへの妊娠前からの糖転移ヘスペリジンの投与は出生仔マウスの免疫レジリエンスを高める 
    受賞者: 鈴木巴乃;ZHU MOHAN;堀井鴻佑;森島真幸
  • 2022年08月 日本病態生理学会 学部学生・修士課程大学院生セッション 優秀賞
     妊娠・授乳期のヘスペリジンの摂取が母子の免疫機能に及ぼす影響 
    受賞者: 松永華奈;山本こはる;堀井鴻佑;森島真幸
  • 2021年03月 日本循環器学会 Circulation Journal誌 年間優秀論文賞(Experimental Investigation)
     
    受賞者: 嶋岡徹*、王岩*、森島真幸*、宮本伸二、小野克重
  • 2014年07月 日本不整脈心電学会 第29回日本不整脈学会学術大会・第31回日本心電学会学術集会合同学術大会 Young Investigator's Award
     
    受賞者: 森島 真幸
  • 2013年08月 日本病態生理学会 第23回日本病態生理学会大会 特別表彰
     
    受賞者: 森島 真幸
  • 2013年07月 第12回九州脳・高血圧・循環制御研究会 最優秀演題賞
     
    受賞者: 森島 真幸
  • 2008年07月 第7回九州脳と高血圧研究会 最優秀賞
     
    受賞者: 森島 真幸
  • 2007年11月 日本心臓財団 第5回日本心臓財団若年研究者研究奨励(藤基金)
     
    受賞者: 森島 真幸
  • 2007年06月 International Society for Heart Research Young Investigator's Award
     
    受賞者: 森島 真幸
  • 2006年02月 徳島大学 康楽賞
     
    受賞者: 森島 真幸
  • 2005年08月 徳島大学, 徳島県医師会 第232回徳島医学会 最優秀演題賞
     
    受賞者: 森島 真幸

共同研究・競争的資金等の研究課題

  • 日本学術振興会:科学研究費助成事業 基盤研究(C)
    研究期間 : 2023年04月 -2026年03月 
    代表者 : 森島 真幸
  • 日本学術振興会:科学研究費助成事業 基盤研究(C)
    研究期間 : 2020年04月 -2023年03月 
    代表者 : 森島 真幸
     
    心房細動の発症や持続は、心筋に発現するイオンチャネル遺伝子の発現異常による電気的リモデリングが重要な原因となるが、その詳細な成立機序については解明されていない。今年度の研究では、高脂肪食を負荷したマウスの心筋障害に対してEPAは保護作用を示すかどうかについて検証した。C57BL/6マウスに60%高脂肪食(HF)を8週間負荷し同時にEPAを8週間経口投与した際の心機能の変化をみた。HF群では有意な体重増加と心筋収縮力の低下が確認されたが、EPAの慢性投与により部分的な改善が認められた。HF群の心房筋、心室筋におけるIL-10, IL-1b, TNF-aのmRNA発現はControl群で有意に増加したが、EPAによる改善効果はIL-10 mRNA発現でのみ認められた。一方、心房筋におけるL型カルシウムチャネルの発現はEPA投与により有意に増加することが判明した。さらに、マウス心筋細胞を用いた細胞免疫染色の結果から、EPAの投与によりCav1.2発現は有意に増加することが確認された。以上の結果から、EPAは高脂肪食負荷により障害を受けた心筋細胞に対して、イオンチャネル遺伝子の発現を増加させることで心筋の電気的リモデリング抑制に作用する可能性が示唆された。
  • microRNA過剰発現ラットの作製とそれを用いた新しい不整脈発症機序の解明
    日本学術振興会:平成27年度科学研究費助成事業 国際共同研究加速基金
    研究期間 : 2016年04月 -2019年03月 
    代表者 : 森島 真幸
  • 日本学術振興会:科学研究費助成事業 基盤研究(C)
    研究期間 : 2015年04月 -2018年03月 
    代表者 : 森島 真幸; 小野 克重
     
    本研究では個体レベルでmicroRNA(miR-30d)が心房細動の病態形成にどのように関わるかを解析する目的で、心筋特異的miR-30d過剰発現ラットを作製した。陽性個体が数匹得られたが、miR-30d陽性のオスはより脆弱で短命であるため継代及び系の樹立に時間を要することがわかった。このため、ラットの作製に並行して細胞内カルシウム過負荷病態モデルを作製し、病態心におけるmiR-30dの発現増加メカニズムの解析と病態形成過程における血漿中miR-30d発現量の定量を行った。その結果、miR-30d発現量は血漿中並びに心房筋において病態の悪化に伴い増加することがわかった。
  • 日本学術振興会:科学研究費助成事業 国際共同研究加速基金(国際共同研究強化)
    研究期間 : 2016年 -2018年 
    代表者 : 森島 真幸; シン ハープリート
     
    我々は、ヒト持続性心房細動患者の心房筋でmicroRNA-30d(miR-30d)が過剰発現することを発見しその発現は細胞内Ca2+過負荷により亢進されることを報告した。しかし、miR-30dの生体内における発現動態は明らかにされていない。そこで本研究では、心筋特異的miR-30d過剰発現ラット、並びに細胞内Ca2+過負荷モデルラットを作成し心臓組織(心房・心室)と循環血中(血漿)のmiR-30d発現量を解析することで、病態心におけるmiR-30dの発現増加メカニズムを明らかにすることを目的とした。
  • 日本学術振興会:科学研究費助成事業 若手研究(B)
    研究期間 : 2012年04月 -2015年03月 
    代表者 : 森島 真幸
     
    我々が構築した世界初の高自発運動モデル動物SPORTSを実験のツールとして用い、運動習慣の制御機構だけでなく、心筋肥大の形成機構を同時に解析することを本事業の目的とした。SPORTSラットにおいては、運動による血圧増加を伴わず生理的な刺激による心筋の成熟機構とは異なる機序で心筋肥大が形成されていることが判明した。さらに、脳内モノアミンは運動習慣の制御のみならず、心拍数制御や心筋の肥大形成に関与することで、自発運動に適応する心臓循環機能を獲得することに貢献する可能性が示唆された。
  • 運動意欲促進の分子メカニズムの解明
    日本学術振興会:平成21年度科学研究費補助金 若手研究(B)
    研究期間 : 2009年04月 -2012年03月 
    代表者 : 森島 真幸
  • 日本学術振興会:科学研究費助成事業 基盤研究(C)
    研究期間 : 2010年 -2012年 
    代表者 : 岩田 英理子; 小野 克重; 森島 真幸
     
    心房細動は最も罹患率が多いにもかかわらず治療戦略がいまだ確立されていない不整脈である。我々は、心臓大血管の手術で体外循環を使用する患者より得られたヒト心房筋(右心耳等)を用いて、慢性心房細動を有する患者の心房筋において発現の変化を認める特定のイオンチャネルと microRNA を同定し、イオンチャネルリモデリングにおけるmicroRNA の関連と治療への応用の可能性を示唆した。
  • 日本学術振興会:科学研究費助成事業 若手研究(B)
    研究期間 : 2009年 -2011年 
    代表者 : 森島 真幸; 中屋 豊
     
    本研究は、生まれつき自発運動への欲求が正常Wistarラットよりも強い自然発症の高運動性モデルラットSPORTS(Spontaneousy Running Tokushjma-Shikoku ; Wistar系)を実験のツールとして用いて、運動意欲の制御に関わる脳内分子基盤の解明を目指すと同時に、心臓自律神経活動への影響を解析することにより、神経性因子を介した自発運動の制御と心機能の連関作用を生理学的に実証することを目的とした。申請者は、これまで脳内モノアミン酸化酵素A(MAOA)の活性低下がラットの自発運動を誘発していることを明らかにしてきた(Morishima et al., Neuropsychopharmacology 2006)。本研究では、安全で有益な運動不足解消法の開発の為に、運動負荷を行う上で心機能の重要なパラメータである心臓自律神経活動の評価を縦列して行う実験系を確立し、脳内モノアミンと心機能解析を同時に行った。その結果、SPORTSラットは安静時において早い心拍を示すが自発運動時には心臓交感神経活動(L/H比)を極度に高めないことを見出した。さらに、対照ラットにモノアミン酸化酵素A(MAOA)阻害薬を投与し脳海馬モノアミン量を定量したところ、SPORTSラットと同程度に海馬ノルエピネフリン放出量が増加し、自発運動量や心拍数の増加が認められた。また、心拍変動解析の結果、MAOA阻害薬投与ラットでは、SPORTSラットと同様に心拍数の増加の認められた夜間活動時間帯で交感神経活動指標であるL/H比が有意に上昇していたが、自発運動により是正されることが判明した。本事業により、自発運動を引き起こす因子(脳内ノルエピネフリン)が生体にとって質的良好な運動基盤分子である可能性が示唆された。本研究の成果は、運動療法を必要とする心疾患患者だけでなく健康な個人に対しても、運動の効果を最大限に発揮できるシステムの開発に貢献することが期待される。
  • 日本学術振興会:科学研究費助成事業 基盤研究(C)
    研究期間 : 2007年 -2008年 
    代表者 : 小野 克重; 小野 克重; 李 泰成; 鄭 明奇; 森島 真幸
     
    心筋細胞におけるT型Ca^(2+)チャネルは自動能の形成作用の他はその機能が知られていなかった。本研究は、僅かな細胞膜電位の変化が窓電流形成膜電位に達することでT型Ca^(2+)チャネルを通過するCa^(2+)電流が細胞内Ca^(2+)過負荷を引き起こし、T型Ca^(2+)チャネルが細胞のアポトーシスの引き金として機能することを初めて明らかにした。
  • アンジオテンシンII受容体を介する心筋イオンチャネルremodelingの分子機序の解明
    日本心臓財団:平成19年度日本心臓財団研究奨励第5回日本心臓財団若年研究者研究奨励(藤基金)
    代表者 : 森島 真幸

委員歴

  • 2022年09月 - 現在   日本病態生理学会   理事
  • 2020年04月 - 現在   日本生理学会   男女共同参画推進委員
  • 2015年07月 - 現在   日本不整脈心電学会   評議員
  • 2015年03月 - 現在   日本生理学会   評議員
  • 2014年08月 - 現在   日本病態生理学会   評議員
  • 2019年03月 - 2022年09月   生理学女性研究者の会   運営委員
  • 2017年03月 - 2019年03月   生理学女性研究者の会   総務企画委員

担当経験のある科目

  • 食品機能学実験I, II (大学院応用生命化学専攻)近畿大学
  • 食品機能学演習(大学院応用生命化学専攻)近畿大学
  • 卒業研究近畿大学
  • 専門演習I, II近畿大学
  • 臨地実習IV(公衆栄養学)近畿大学
  • 微生物学実験近畿大学
  • 公衆栄養学実習近畿大学
  • 公衆栄養学I近畿大学
  • 公衆栄養学II近畿大学
  • 応用栄養学大分大学,徳島大学
  • 生理学大分大学
  • 生理学実習大分大学

社会貢献活動

  • 男性にとってのワークライフバランスと若者たちの思い ~男女共に共存できる環境とは~
    期間 : 2024年03月28日 - 2024年03月28日
    役割 : 司会
    種別 : セミナー・ワークショップ
    主催者・発行元 : 日本生理学会男女共同参画推進委員会
    イベント・番組・新聞雑誌名 : 第101回日本生理学会大会男女共同参画推進委員会企画ランチョンシンポジウム
  • コロナ禍がもたらした健康への新たなアプローチ ~身近な食材に存在する天然酵母を観察してみよう~
    期間 : 2022年10月28日
    役割 : 出演
    種別 : 出前授業
    主催者・発行元 : 近畿大学農学部
    イベント・番組・新聞雑誌名 : 近畿大学農学部キャンパス見学会(附属東広島中学校)
  • キャンパス発この一品「未利用食材活用のふりかけ―近畿大」
    期間 : 2022年03月16日
    役割 : 出演
    種別 : 新聞・雑誌
    主催者・発行元 : 日本経済新聞
    イベント・番組・新聞雑誌名 : 日本経済新聞

その他

  • 2021年08月 - 2022年03月  令和3年度”オール近大”新型コロナウイルス感染症対策支援プロジェクト 研究提案代表者 
    規格外食材を利用したポストコロナ時代の食環境整備
  • 2020年06月 - 2021年03月  令和2年度”オール近大”新型コロナウイルス感染症支援プロジェクト 研究提案代表者 
    「近大ふりかけ」の開発~ウイルスに負けない身体づくり・やる気をアップさせる「ふりかけ」を全国の食卓に~

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