Identification of endogenous inhibitors of CF6, a novel hypertensive substance, and their application to drug discovery.

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K08573
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Hirosaki Gakuin University
• Principal Investigator: Tanaka Makoto 弘前学院大学, 看護学部, 准教授 (10720873)
• Co-Investigator(Kenkyū-buntansha): 長内 智宏 弘前大学, 保健学研究科, 教授 (00169278)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: アラキドン酸 / Coupling factor 6(CF6) / プロスタサイクリン / 一酸化窒素

Outline of Final Research Achievements

We examined the effect of CF6 on the inhibition of prostacyclin production. Arachidonic acid release from CF6-overexpressing TG mouse fibroblasts was significantly decreased compared to WT cells. It was significantly increased by overexpression of the inhibitory protein IF1. We investigated the effect of IF1 on NO production. Under acetylcholine stimulation, NO production in TG cells was significantly decreased compared to WT cells. Overexpression of IF1 restored NO production in TG cells to almost the same level as in WT cells. Serin-1177 phosphorylation of eNOS was observed in TG cells overexpressing IF1. This suggests that IF1 cancels the decrease in NO production by CF6.

Free Research Field

基礎医学

Academic Significance and Societal Importance of the Research Achievements

CF6はF1分子モーターを活性化しプロスタサイクリン産生の抑制、食塩感受性高血圧ならびに糖尿病の発症を引き起こす。このF1分子モーターを阻害する物質としてInhibitory protein IF1が同定された。IF1の有用性の検討は、心血管系における病態生理学的意義の解明並びに創薬を考えた上で極めて重要である。また、IF1投与によるCF6の細胞内情報伝達機構への影響の解明は、心疾患を初めとした循環器疾患の形成にCF6がどのように関与するかを明らかにできる点で学術的な特色と独創性がある。