| Project/Area Number |
23591085
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
TANNO Masaya 札幌医科大学, 医学部, 講師 (00398322)
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| Co-Investigator(Kenkyū-buntansha) |
MIURA Tetsuji 札幌医科大学, 医学部, 教授 (90199951)
HORIO Yoshiyuki 札幌医科大学, 医学部, 教授 (30181530)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 心不全 / SIRT1 / 酸化ストレス / 糖尿病 / 細胞死 |
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| Research Abstract |
Nuclear translocation of SIRT1 suppresses cardiomyocyte death in failing hearts. We demonstrated that phosphorylation of Ser517 of SIRT1 by Akt/PI3K contributed to the nuclear translocation. Furthermore, we identified proteins whose binding to SIRT1 change during oxidative stress, using immunoprecipitation, 2D gel electrophoresis and mass spectrometry. The physiological significance of the protein-protein interaction is currently under investigation. To translate the cardioprotective function of activation or nuclear translocation of SIRT1, we first analyzed a characteristics of OLETF rats, obese insulin-resistant type 2 diabetes rats, as an in vivo animal model for heart failure. In this model, diastolic dysfunction was induced under pressure overload, but not physiological conditions, and the mechanisms that trigger the functional impairment was explored in detail. We are currently investigating whether and how SIRT1 modifies the development of diastolic dysfunction.
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