KINDAI UNIVERSITY


*A space between the first name and last name, please enter

NAKAMURA Kyoko

Profile

FacultyPharmaceutical Research and Technology Institute
PositionLecturer
Degree
Commentator Guidehttps://www.kindai.ac.jp/meikan/742-nakamura-kyouko.html
URL
Mail
Last Updated :2020/09/30

Education and Career

Academic & Professional Experience

  •   2013 , Faculty of Medicine, Kindai University

Research Activities

Research Areas

  • Life sciences, Nutrition and health science
  • Life sciences, Metabolism and endocrinology

Research Interests

  • IGFBP-1, SHRSP

Published Papers

  • Changes of endothelium-dependent vasodilation in aortae from obese and non-obese type 2 diabetic rats and the roles of hyperglycemia/hyperosmolarity., Chin. J. Hypertens., Chin. J. Hypertens., 19(6), 529 - 537, Jun. 2011 , Refereed
  • Cell-cycle arrest in mature adipocytes impairs BAT development but not WAT browning, and reduces adaptive thermogenesis in mice, Yuko Okamatsu-Ogura, Keigo Fukano, Ayumi Tsubota, Junko Nio-Kobayashi, Kyoko Nakamura, Masami Morimatsu, Hiroshi Sakaue, Masayuki Saito, Kazuhiro Kimura, SCIENTIFIC REPORTS, SCIENTIFIC REPORTS, 7(1), Jul. 2017 , Refereed
    Summary:We previously reported brown adipocytes can proliferate even after differentiation. To test the involvement of mature adipocyte proliferation in cell number control in fat tissue, we generated transgenic (Tg) mice over-expressing cell-cycle inhibitory protein p27 specifically in adipocytes, using the aP2 promoter. While there was no apparent difference in white adipose tissue (WAT) between wild-type (WT) and Tg mice, the amount of brown adipose tissue (BAT) was much smaller in Tg mice. Although BAT showed a normal cellular morphology, Tg mice had lower content of uncoupling protein 1 (UCP1) as a whole, and attenuated cold exposure-or beta 3-adrenergic receptor (AR) agonist-induced thermogenesis, with a decrease in the number of mature brown adipocytes expressing proliferation markers. An agonist for the beta 3-AR failed to increase the number of proliferating brown adipocytes, UCP1 content in BAT, and oxygen consumption in Tg mice, although the induction and the function of beige adipocytes in inguinal WAT from Tg mice were similar to WT mice. These results show that brown adipocyte proliferation significantly contributes to BAT development and adaptive thermogenesis in mice, but not to induction of beige adipocytes.
  • Effect of electrolyzed water produced using carbon electrodes on HeLa cell proliferation, Kyoko Nakamura, Osamu Muraoka, BioScience Trends, BioScience Trends, 11(6), 688 - 693, 2017 , Refereed
    Summary:We developed electrolyzed water (EW) using carbon electrodes and investigated the ability of the developed EW to inhibit the proliferation of human cervical carcinoma HeLa cells. We observed that EW-containing media inhibited HeLa cell proliferation. Many very small black dots were produced in EW and these were associated with the inhibitory effect on the cell proliferation. Furthermore, the very small black dots that could inhibit cell proliferation were produced only at pH 3 to 3.5 of EW. Additional experiments showed that this inhibition of proliferation is reversible. These results suggest that the effect of EW on HeLa cells is cytostatic and not cytotoxic. Thus, our results indicate that the EW developed in this study may be used to inhibit cell proliretation.
  • Proliferative and Antiapoptotic Signaling Stimulated by Nuclear-Localized PDK1 Results in Oncogenesis, Chintan K. Kikani, Erik V. Verona, Jiyoon Ryu, Yanying Shen, Qingqing Ye, Li Zheng, Ziliang Qian, Hiroshi Sakaue, Kyoko Nakamura, Jie Du, Qunsheng Ji, Wataru Ogawa, Lu-Zhe Sun, Lily Q. Dong, Feng Liu, SCIENCE SIGNALING, SCIENCE SIGNALING, 5(249), Nov. 2012 , Refereed
    Summary:Enhanced activation of phosphoinositide 3-kinase (PI3K) is a hallmark of many human tumors because it promotes cell proliferation and survival through several mechanisms. One of these mechanisms is the phosphorylation of the serine and threonine kinase Akt at the cytosolic side of the plasma membrane by phosphoinositide-dependent protein kinase 1 (PDK1), which is recruited and activated by binding to the phosphoinositides produced by PI3K. We previously demonstrated increased nuclear accumulation of PDK1 in cells with enhanced PI3K activity. We report that nuclear PDK1 promoted cell proliferation by suppressing FOXO3A-dependent transcription of the gene encoding p27(Kip1) (an inhibitor of cell cycle progression), whereas it enhanced cell survival by inhibiting the activation of c-Jun amino-terminal kinase. Cells with nuclear-localized PDK1 showed anchorage-independent growth, and when injected into mice, these cells induced the formation of solid tumors. In human prostate tumors, cytoplasmic localization of PDK1 correlated only with early-stage, low-risk tumors, whereas nuclear PDK1 localization correlated with high-risk tumors. Together, our findings suggest a role for nuclear-translocated PDK1 in oncogenic cellular transformation and tumor progression in mice and humans.
  • Differential Changes of Aorta and Carotid Vasodilation in Type 2 Diabetic GK and OLETF Rats: Paradoxical Roles of Hyperglycemia and Insulin, Mei-Fang Zhong, Wei-Li Shen, Masaki Tabuchi, Kyoko Nakamura, Yi-Chen Chen, Cong-Zhen Qiao, Jin He, Jie Yang, Chuan Zhang, Zdravko Kamenov, Hideaki Higashino, Hong Chen, EXPERIMENTAL DIABETES RESEARCH, EXPERIMENTAL DIABETES RESEARCH, 2012 , Refereed
    Summary:We investigated large vessel function in lean Goto-Kakizaki diabetic rats (GK) and Otsuka Long-Evans Tokushima Fatty diabetic rats (OLETF) with possible roles of hyperglycemia/hyperosmolarity and insulin. Both young and old GK showed marked hyperglycemia with normal insulin level and well-preserved endothelium-dependent and endothelium-independent vasodilation in aorta and carotid artery. There were significant elevations in endothelial/inducible nitric oxide synthase (eNOS/iNOS) and inducible/constitutive heme oxygenase (HO-1/HO-2) in GK. The endothelium-dependent vasodilation in GK was inhibited partly by NOS blockade and completely by simultaneous blocking of HO and NOS. In contrast, OLETF showed hyperinsulinemia and mild hyperglycemia but significant endothelium dysfunction beginning at early ages with concomitantly reduced eNOS. Insulin injection corrected hyperglycemia in GK but induced endothelium dysfunction and intima hyperplasia. Hyperglycemia/hyperosmolarity in vitro enhanced vessel eNOS/HO. We suggest that hyperinsulinemia plays a role in endothelium dysfunction in obese diabetic OLETF, while hyperglycemia/hyperosmolarity-induced eNOS/HO upregulation participates in the adaptation of endothelium function in lean diabetic GK.
  • Differential Changes of Aorta and Carotid Vasodilation in Type 2 Diabetic GK and OLETF Rats: Paradoxical Roles of Hyperglycemia and Insulin, Mei-Fang Zhong, Wei-Li Shen, Masaki Tabuchi, Kyoko Nakamura, Yi-Chen Chen, Cong-Zhen Qiao, Jin He, Jie Yang, Chuan Zhang, Zdravko Kamenov, Hideaki Higashino, Hong Chen, EXPERIMENTAL DIABETES RESEARCH, EXPERIMENTAL DIABETES RESEARCH, 2012, 42902, 2012 , Refereed
    Summary:We investigated large vessel function in lean Goto-Kakizaki diabetic rats (GK) and Otsuka Long-Evans Tokushima Fatty diabetic rats (OLETF) with possible roles of hyperglycemia/hyperosmolarity and insulin. Both young and old GK showed marked hyperglycemia with normal insulin level and well-preserved endothelium-dependent and endothelium-independent vasodilation in aorta and carotid artery. There were significant elevations in endothelial/inducible nitric oxide synthase (eNOS/iNOS) and inducible/constitutive heme oxygenase (HO-1/HO-2) in GK. The endothelium-dependent vasodilation in GK was inhibited partly by NOS blockade and completely by simultaneous blocking of HO and NOS. In contrast, OLETF showed hyperinsulinemia and mild hyperglycemia but significant endothelium dysfunction beginning at early ages with concomitantly reduced eNOS. Insulin injection corrected hyperglycemia in GK but induced endothelium dysfunction and intima hyperplasia. Hyperglycemia/hyperosmolarity in vitro enhanced vessel eNOS/HO. We suggest that hyperinsulinemia plays a role in endothelium dysfunction in obese diabetic OLETF, while hyperglycemia/hyperosmolarity-induced eNOS/HO upregulation participates in the adaptation of endothelium function in lean diabetic GK.
  • Overexpression of KLF15 Transcription Factor in Adipocytes of Mice Results in Down-regulation of SCD1 Protein Expression in Adipocytes and Consequent Enhancement of Glucose-induced Insulin Secretion, Tomoki Nagare, Hiroshi Sakaue, Michihiro Matsumoto, Yongheng Cao, Kenjiro Inagaki, Mashito Sakai, Yasuhiro Takashima, Kyoko Nakamura, Toshiyuki Mori, Yuko Okada, Yasushi Matsuki, Eijiro Watanabe, Kazutaka Ikeda, Ryo Taguchi, Naomi Kamimura, Shigeo Ohta, Ryuji Hiramatsu, Masato Kasuga, JOURNAL OF BIOLOGICAL CHEMISTRY, JOURNAL OF BIOLOGICAL CHEMISTRY, 286(43), 37458 - 37469, Oct. 2011 , Refereed
    Summary:Kruppel-like factor 15 (KLF15), a member of the Kruppel-like factor family of transcription factors, has been found to play diverse roles in adipocytes in vitro. However, little is known of the function of KLF15 in adipocytes in vivo. We have now found that the expression of KLF15 in adipose tissue is down-regulated in obese mice, and we therefore generated adipose tissue-specific KLF15 transgenic (aP2-KLF15Tg) mice to investigate the possible contribution of KLF15 to various pathological conditions associated with obesity in vivo. The aP2-KLF15 Tg mice manifest insulin resistance and are resistant to the development of obesity induced by maintenance on a high fat diet. However, they also exhibit improved glucose tolerance as a result of enhanced insulin secretion. Furthermore, this enhancement of insulin secretion was shown to result from down-regulation of the expression of stearoyl-CoA desaturase 1 (SCD1) in white adipose tissue and a consequent reduced level of oxidative stress. This is supported by the findings that restoration of SCD1 expression in white adipose tissue of aP2-KLF15 Tg mice exhibited increased oxidative stress in white adipose tissue and reduced insulin secretion with hyperglycemia. Our data thus provide an example of cross-talk between white adipose tissue and pancreatic beta cells mediated through modulation of oxidative stress.
  • Effects of Gorei-san: A traditional Japanese Kampo medicine, on aquaporin 1, 2, 3, 4 and V2R mRNA expression in rat kidney and forebrain, T. Kurita, K. Nakamura, M. Tabuchi, M. Orita, K. Ooshima, H. Higashino, Journal of Medical Sciences, Journal of Medical Sciences, 11(1), 30 - 38, 2011 , Refereed
    Summary:The details of pharmacological mechanisms of Gorei-san, a traditional Japanese Kampo medicine, remains to be clarified, although it has been used for diuretic and hydrostatic purposes. From these circumstances, the effects of this medicine on the expressions of aquaporin (AQP) 1, 2, 3, 4 and vasopressin 2 receptor (V2R) mRNAs were investigated in relation to diuresis and water balance regulation in the kidney and brain. Gorei-san extract decocted with hot water was given to rats loaded with 50 mL kg-1 volume of physiological saline and AQP1, 2, 3, 4 and V2R mRNAs were measured with real-time polymerase chain reaction (PCR) in the cortex and the medulla of kidney and the forebrain. A low dose of Gorei-san extract (100 mg kg-1) led to an increase in urine excretion and lower AQP3 mRNA expression in the cortex as well as lower expression of AQP2 and AQP3 mRNAs in the medulla of kidney, whereas no change in V2R mRNA expression was observed. AQP1 mRNA expression decreased in the forebrain of rats loaded with an excess volume of physiological saline compared with rats not loaded with excess saline and given no agent. A low dose of Gorei-san extract increased urine excretion volume, probably due to the downregulation of AQP3 mRNA in the cortex and downregulation of AQP2 and AQP3 mRNAs in the medulla of the kidney, in which changes were not related to V2R mRNA expression. An excess volume of physiological saline given to rats caused an inhibition of AQP1 mRNA expression in the forebrain, which probably functioned to maintain the water balance in a hyper-hydrous state.
  • PDK1 regulates cell proliferation and cell cycle progression through control of cyclin D1 and p27(Kip1) expression, Kyoko Nakamura, Hiroshi Sakaue, Akihiko Nishizawa, Yasushi Matsuki, Hideyuki Gomi, Eijiro Watanabe, Ryuji Hiramatsu, Mimi Tamamori-Adachi, Shigetaka Kitajima, Tetsuo Noda, Wataru Ogawa, Masato Kasuga, JOURNAL OF BIOLOGICAL CHEMISTRY, JOURNAL OF BIOLOGICAL CHEMISTRY, 283(25), 17702 - 17711, Jun. 2008 , Refereed
    Summary:PDK1 (3-phosphoinositide-dependent protein kinase 1) is a key mediator of signaling by phosphoinositide 3-kinase. To gain insight into the physiological importance of PDK1 in cell proliferation and cell cycle control, we established immortalized mouse embryonic fibroblasts (MEFs) from mice homozygous for a "floxed" allele of Pdk1 and from wild-type mice. Introduction of Cre recombinase by retrovirus-mediated gene transfer resulted in the depletion of PDK1 in Pdk1(lox/lox) MEFs but not in Pdk1(+/+) MEFs. The insulin-like growth factor-1-induced phosphorylation of various downstream effectors of PDK1, including Akt, glycogen synthase kinase 3, ribosomal protein S6, and p70 S6 kinase, was markedly inhibited in the PDK1-depleted (Pdk1-KO) MEFs. The rate of serum-induced cell proliferation was reduced; progression of the cell cycle from the G(0)-G(1) phase to the S phase was delayed, and cell cycle progression at G(2)-M phase was impaired in Pdk1-KO MEFs. These cells also manifested an increased level of p27(Kip1) expression and a reduced level of cyclin D1 expression during cell cycle progression. The defect in cell cycle progression from the G(0)-G(1) to the S phase in Pdk1-KO MEFs was rescued by forced expression of cyclin D1, whereas rescue of the defect in G(2)-M progression in these cells required both overexpression of cyclin D1 and depletion of p27(Kip1) by RNA interference. These data indicate that PDK1 plays an important role in cell proliferation and cell cycle progression by controlling the expression of both cyclin D1 and p27(Kip1).
  • Fused protein of delta PKC activation loop and PDK1-interacting fragment (delta AL-PIF) functions as a pseudosubstrate and an inhibitory molecule for PDK1 when expressed in cells, Takahiro Seki, Naoki Irie, Kyoko Nakamura, Hiroshi Sakaue, Wataru Ogawa, Masato Kasuga, Hideyuki Yamamoto, Shiho Ohmori, Naoaki Saito, Norio Sakai, GENES TO CELLS, GENES TO CELLS, 11(9), 1051 - 1070, Sep. 2006 , Refereed
    Summary:To elucidate the role of 3-phosphoinositide-dependent protein kinase-1 (PDK1) in cellular signaling, we constructed and expressed a pseudosubstrate of PDK1, designated as delta AL-PIF, and characterized its properties in cultured cells. delta AL-PIF consists of two fused proteins of the protein kinase C delta (delta PKC) activation loop (delta AL) and PDK1-interacting fragment (PIF). The phosphorylation of delta AL-PIF was detected with anti-delta PKC phospho-Thr(505)-specific antibody and was increased in proportion to the expression level of co-expressed GST-PDK1, indicating that it acts as a pseudosubstrate of PDK1. In cells expressing delta AL-PIF, basal phosphorylation level at the activation loop of PKB alpha, delta PKC and gamma PKC was reduced, compared with that in control cells, suggesting that delta AL-PIF functions as an inhibitory molecule for PDK1. delta AL-PIF affected the stability, translocation and endogenous activity of PKCs. These effects of delta AL-PIF on gamma PKC properties were confirmed by investigation using conditioned PDK1 knockout cells. Furthermore, apoptosis frequently occurred in cells expressing delta AL-PIF for 3 days. These findings revealed that delta AL-PIF served as an effective pseudosubstrate and an inhibitory molecule for PDK1, suggesting that this molecule can be used as a tool for investigating PDK-mediated cellular functions as well as being applicable for anti-cancer therapy.

Misc

  • Role of krüppel-like factor 15 (KLF15) in transcriptional regulation of adipogenesis, Toshiyuki Mori, Hiroshi Sakaue, Hiroshi Sakaue, Haruhisa Iguchi, Hideyuki Gomi, Yuko Okada, Yasuhiro Takashima, Kyoko Nakamura, Takehiro Nakamura, Toshimasa Yamauchi, Naoto Kubota, Takashi Kadowaki, Yasushi Matsuki, Wataru Ogawa, Ryuji Hiramatsu, Masato Kasuga, Journal of Biological Chemistry, 280, 12867, 12875,   2005 04 01 , 10.1074/jbc.M410515200, https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=20144387014&origin=inward
    Summary:Krüppel-like zinc finger transcription factors (KLFs) play diverse roles during cell differentiation and development in mammals. We have now shown by microarray analysis that expression of the KLF15 gene is markedly up-regulated during the differentiation of 3T3-L1 preadipocytes into adipocytes. Inhibition of the function of KLF15, either by expression of a dominant negative mutant or by RNA interference, both reduced the expression of peroxisome proliferator-activated receptor γ (PPARγ) and blocked adipogenesis in 3T3-L1 preadipocytes exposed to inducers of adipocyte differentiation. However, the dominant negative mutant of KLF15 did not affect the expression of CCAAT/enhancer-binding protein β (C/EBPβ) elicited by inducers of differentiation in 3T3-L1 preadipocytes. In addition, ectopic expression of KLF15 in NIH 3T3 or C2C12 cells triggered both lipid accumulation and the expression of PPARγ in the presence of inducers of adipocyte differentiation. Ectopic expression of C/EBPβ, C/EBPδ, or C/EBPα in NIH 3T3 cells also elicited the expression of KLF15 in the presence of inducers of adipocyte differentiation. Moreover, KLF15 and C/EBPα acted synergistically to increase the activity of the PPARγ2 gene promoter in 3T3-L1 adipocytes. Our observations thus demonstrate that KLF15 plays an essential role in adipogenesis in 3T3-L1 cells through its regulation of PPARγ expression. © 2005 by The American Society for Biochemistry and Molecular Biology, Inc.
  • Role of MAPK phosphatase-1 (MKP-1) in adipocyte differentiation, Hiroshi Sakaue, Wataru Ogawa, Wataru Ogawa, Takehiro Nakamura, Toshiyuki Mori, Kyoko Nakamura, Masato Kasuga, Journal of Biological Chemistry, 279, 39951, 39957,   2004 09 17 , 10.1074/jbc.M407353200, https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=4544222907&origin=inward
    Summary:Both time-dependent modulation of intracellular signaling molecules and sequential induction of transcriptional regulators are essential for the differentiation of preadipocytes into adipocytes. We have now shown that the activity, but not the abundance, of p42/p44 mitogen-activated protein kinase (MAPK) is down-regulated during adipocyte differentiation. This decrease in p42/p44 MAPK activity does not appear to be a direct effect of hormonal inducers of differentiation but rather represents a characteristic event of adipocyte differentiation that is achieved through a persistent change in intracellular signaling. Although the phosphorylation or abundance of MEK, an upstream kinase for p42/p44 MAPK, was not altered during differentiation, the abundance of MAPK phosphatase-1 (MKP-1), a negative regulator of p42/p44 MAPK, was increased with a time course similar to that of the down-regulation of p42/p44 MAPK activity. Ectopic expression of MKP-1 in preadipocytes reduced and depletion of endogenous MKP-1 in mature adipocytes increased the activity of p42/p44 MAPK. Prevention of the up-regulation of MKP-1 abundance in preadipocytes by expression of Mkp-1 antisense RNA resulted in persistence of p42/p44 MAPK activation and blocked differentiation, effects that were reversed by the MEK inhibitor PD98059. These results suggest that MKP-1 plays an essential role in adipocyte differentiation through down-regulation of p42/p44 MAPK activity.
  • Effects of adiponectin on spontaneous stroke in rats, Masaki Tabuchi, Kana Ooshima, Hiroshi Sakaue, Kyoko Nakamura, Atsuko Niwa, Hideo Takahashi, JOURNAL OF PHARMACOLOGICAL SCIENCES, 118, 85P, 85P,   2012