2022 Fiscal Year Final Research Report
Activation of SIRT1 promotes membrane resealing
| Project/Area Number |
21K15629
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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 51030:Pathophysiologic neuroscience-related
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
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| Project Period (FY) |
2021-04-01 – 2023-03-31
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| Keywords | 細胞膜修復 / SIRT1 / CTTN / 骨格筋 / 筋ジストロフィー |
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| Outline of Final Research Achievements |
Resveratrol, an activator of SIRT1, ameliorates muscular function in muscular dystrophy patients, although its mechanism is still not fully elucidated. Here, we investigated the effects of resveratrol on membrane resealing. We found that resveratrol promoted membrane repair in C2C12 cells via the activation of SIRT1. Treatment with resveratrol promoted actin accumulation at the injured site. We also examined the role of cortactin in membrane resealing. Cortactin accumulated at the injury site, and cortactin knockdown suppressed membrane resealing and reorganization of the cytoskeleton. Additionally, SIRT1 deacetylated cortactin and promoted the interaction between cortactin and F-actin, thus possibly enhancing the accumulation of cortactin at the injury site. Finally, we performed a membrane repair assay using single fiber myotubes from control and resveratrol-fed mice. These findings suggest that resveratrol promotes membrane repair via the SIRT1/cortactin axis.
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| Free Research Field |
骨格筋
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| Academic Significance and Societal Importance of the Research Achievements |
本研究によりSIRT1活性化薬であるレスベラトロールが，筋ジストロフィーをはじめとする筋疾患に対して有用であるメカニズムに骨格筋の細胞膜修復が関与する可能性が示された．現在，膜修復を標的とした薬剤の臨床応用はされておらず，新規メカニズムの薬剤開発において重要な知見であると考える．特に今回使用したレスベラトロールについては，我々が既に筋ジストロフィー患者への安全性および効果について報告した薬剤であり，今後は，大規模での臨床試験実施が望まれる．
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