Analysis of circadian rhythm regulated by nitric oxide (NO) or Carbon monoxide (CO)

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K01917
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biomolecular chemistry
• Research Institution: Kyoto Prefectural University
• Principal Investigator: SAGAMI IKUKO 京都府立大学, 生命環境科学研究科, 研究員 (10143033)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 体内時計 / 時計遺伝子 / CO / NO / 転写因子 / ヘムタンパク質

Outline of Final Research Achievements

We analyzed the effects of CO or NO on expression rhythms of endogenous clock genes using real-time circadian gene reporter studies. We found that the CO treatment of the cells at 24 h after the synchronization resulted in the forward phase-shifts of the Per2 and Bmal1 expression rhythms with different modes. The Chip analysis revealed that the CO significantly inhibited the binding of NPAS2 to the E-boxes of Per2 gene, indicating the regulation of circadian rhythms by CO via NPAS2. Interestingly, the NO treatment resulted in the reverse effects on the Per2 and Bmal1 expression rhythms, suggesting that mammalian clock was differently regulated by CO and/or NO signaling system.

Free Research Field

生物化学

Academic Significance and Societal Importance of the Research Achievements

体内時計は高血圧や糖尿病、肥満などの生活習慣病発症や季節的な精神活動の低下と関連する。したがって、本研究によるガス小分子による時計制御分子機構の解明は、 新たな体内時計の制御システム構築の可能性を含み、体内時計の変調が原因となる疾患やその治療法や健康問題の解決に大きく貢献する事が期待出来る。さらに、時計制御因子にCOやNOと同様の構造変化/機能制御を誘起しうる小分子治療薬の開発に役立てることが期待される。