Analysis of a novel mechanism responsible for postmenopausal hypertension

• Project/Area Number: 23590296
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Chiba University
• Principal Investigator: KIMURA Sadao 千葉大学, 医学(系)研究科(研究院), 教授 (40134225)
• Co-Investigator(Kenkyū-buntansha): NISHIYAMA Mariko 千葉大学, 大学院医学研究院, 助教 (00092081) ; USUI Hirokazu 千葉大学, 大学院医学研究院, 講師 (90375634)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 閉経後高血圧 / アンジオテンシン / アンジオテンシン受容体 / RGS / スピノフィリン / 「国際情報交換」 / 国際情報交流

Research Abstract

This study showed that (1) RGS2 and spinophilin (SPL) are present in vascular smooth muscle cells, (2) RGS2 showed potent inhibitory effects on intracellular calcium responses induced by Ang II in HEK293T cells stably expressing AT1 receptors, (3) SPL strongly enhanced the inhibitory effects of RGS2 on AT1 receptor calcium signaling, and (4) estrogen increased the expression of SPL in vascular smooth muscle cells. These results strongly suggests that loss of circulating estrogen in blood decreases the expression of SPL in smooth muscle cells, and the decreased expression of SPL weakens the inhibitory effects of RGS2 enhanced by SPL, leading to the development of hypertension in postmenopausal women.

Research Products

• [Journal Article] Brefeldin A is an estrogenic, Erk1/2-activating component in the extract of Agaricus blazei mycelia. (2013)
  • Author(s): Dong S1, Furutani Y, Kimura S, Zhu Y, Kawabata K, Furutani M, Nishikawa T, Tanaka T, Masaki T, Matsuoka R, Kiyama R
  • Journal Title: J Agric Food Chem Volume: 61 Issue: 1 Pages: 128-136
  • DOI: 10.1021/jf304546a
  • Peer Reviewed
• [Journal Article] Mechanism for p38α-mediated experimental autoimmune encephalomyelitis (2012)
  • Author(s): Namiki, K., Matsunaga, H., Yoshioka, K., Tanaka, K., Murata, K., Ishida, J
  • Journal Title: J. Biol. Chem Volume: 287 Issue: 29 Pages: 24228-24238
  • DOI: 10.1074/jbc.m111.338541
  • Peer Reviewed
• [Journal Article] Glucagon-like peptide-1 secretion by direct stimulation of L cells with luminal sugar versus non-nutritive sweetener (2012)
  • Author(s): Sakurai, K., Lee, EY., Morita, A., Kimura, S., Kawamura, H., Kasamatsu, A.,Shiiba, M., Yabe, D., Yokote,K., Miki, T
  • Journal Title: J Diabetes Invest Volume: 3 Issue: 2 Pages: 156-63
  • DOI: 10.1111/j.2040-1124.2011.00163.x
  • Peer Reviewed
• [Journal Article] Potent and selective inhibition of angiotensin AT1 receptor signalling by RGS2: roles of its N-terminal domain (2011)
  • Author(s): Matsuzaki N, Nishiyama M, Song D, Moroi K, Kimura S
  • Journal Title: Cellular Signalling Volume: Vol.23、No.6 Issue: 6 Pages: 1041-1049
  • DOI: 10.1016/j.cellsig.2011.01.023
  • Peer Reviewed
• [Presentation] 血管作動性ペプチド受容体のカルシウム応答に対するRGS8の強力な抑制効果:RGSドメインのC末端部分の需要性 (2014)
  • Author(s): 西山眞理子, 住宮菜弥香, 木村定雄
  • Organizer: 第87回日本薬理学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2014-03-20
• [Presentation] 血管作動性ペプチド受容体のカルシウム応答に対するRGS8の強力な抑制効果： RGSドメインのC末端部分の重要性 (2014)
  • Author(s): 西山眞理子、住宮菜弥香、木村定雄
  • Organizer: 日本薬理学会
  • Place of Presentation: 仙台国際センター
• [Presentation] 血管作動性ペプチド受容体のカルシウム応答に対するRGS2, RGS3, RGS8の強力な抑制効果 (2012)
  • Author(s): 宋丹, 西山眞理子, 木村定雄
  • Organizer: 第85回日本薬理学会総会
  • Place of Presentation: 京都
  • Year and Date: 2012-03-14
• [Presentation] 血管作動性ペプチド受容体のカルシウム応答に対するRGS2、RGS3及びRGS8の強力な抑制効果 (2012)
  • Author(s): 宋丹、西山眞理子、木村定雄
  • Organizer: 日本薬理学会年会
  • Place of Presentation: 京都国際会館
• [Presentation] 肺由来幹／前駆細胞(PSPC)の簡便な死守方法の検討
  • Author(s): 田中健介、藤田哲雄、吉岡健人、荻原昌彦、木村定雄、巽浩一郎、粕谷善俊
  • Organizer: 第86回日本薬理学会年会
  • Place of Presentation: 福岡国際会議場
• [Presentation] 小林健、天野寛之、田中健介、吉岡健人、木村定雄、巽浩一郎、粕谷善俊
  • Author(s): 肺線維症の病態進展と蛋白質リン酸化シグナル
  • Organizer: 第86回日本薬理学会年会
  • Place of Presentation: 福岡国際会議場
• [Book] In silico search for biologically active peptides. in "Handbook of the Biologically Active Peptides", 2nd edition(edited by Kastin AJ) (2013)
  • Author(s): Nishiyama M, Ishii M, Hirose S, Yamasaki H, Kimura S
  • Publisher: Academic Press(Chapter 239)
• [Book] Handbook of the Biologically Active Peptides (2013)
  • Author(s): Nishiyama M, Ishii M, Hirose S, Yamasaki H, Kimura S
  • Publisher: Academic Press
• [Remarks]
  • URL: http://www.m.chiba-u.ac.jp/class/bunsiseitai/index.html
• [Remarks] 千葉大学大学院医学研究院分子生体制御学のホームページ（研究課題）
  • URL: http://www.m.chiba-u.ac.jp/class/bunsiseitai/research-new.htm