2020 Fiscal Year Final Research Report
Role of a clock gene DEC1 in the regulation of endothelial NO synthase
| Project/Area Number |
19K17565
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53020:Cardiology-related
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| Research Institution | Hiroshima University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2021-03-31
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| Keywords | 時計遺伝子 / DEC1 / 内皮型NO合成酵素 / AMPK |
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| Outline of Final Research Achievements |
We investigated whether DEC1, one of the clock proteins, is associated with the regulation of the phosphorylation of endothelial nitric oxide synthase (eNOS) through LKB1/AMPK pathway. Endothelial cells were isolated from male Dec1-/- mice and wild-type mice at 6 weeks of age. Phosphorylation and expression of LKB1, AMPK, and eNOS were investigated using Western blot analysis. Western blot analyses revealed that the LKB1 phosphorylation, AMPK phosphorylation, and eNOS phosphorylation were significantly increased in endothelial cells of Dec1-/- mice than in endothelial cells of wild-type mice, whereas there were no significant differences in the LKB1 protein expression, AMPK protein expression, or eNOS protein expression. These finding suggest that DEC1 inhibition increases the eNOS phosphorylation through the increase in LKB1/AMPK phosphorylation.
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| Free Research Field |
血管内皮機能
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、DEC1抑制がeNOSリン酸化亢進に関与している可能性が示された。eNOSリン酸化にはさまざまなシグナリングが関わっているが、DEC1がeNOSリン酸化制御に関わっていることはこれまで報告されておらず、eNOS制御の新規機序の解明につながる可能性がある。
抑制的時計遺伝子Dec1は、時計遺伝子系からの調整だけではなく、光照射や食事、低酸素による調整も受けており、シフトワーカーや睡眠障害者の血圧上昇・心血管疾患発症リスク成因の一部を説明できる可能性があり、さらに血管機能障害に対する予防法や治療法を分子時計系の視点から提唱できる可能性がある。
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