| Project/Area Number |
26461132
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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 |
Cardiovascular 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) |
三木 隆幸 札幌医科大学, 医学部, 准教授 (00336405)
三浦 哲嗣 札幌医科大学, 医学部, 教授 (90199951)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | ミトコンドリア透過性遷移孔 / 細胞死 / グリコーゲン合成酵素キナーゼ3beta / グリコーゲン合成酵素キナーゼ3β / GSK-3β |
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| Outline of Final Research Achievements |
We investigated the molecular mechanisms by which activity of GSK-3beta promotes opening of mitochondrial permeability transition pore (mPTP). The experiments yielded the following results:
(1) Interaction of GSK-3beta with voltage dependent anion channel 2 mediate mitochondrial translocation of GSK-3beta. (2) Lysine 15 at the N terminus of GSK-3beta plays an important role in the function of N-terminal region as a mitochondria targeting signal. (3) ERK and Akt, upstream kinases of GSK-3beta, translocate to the mitochondria and are dephosphorylated in response to oxidative stress. (4) Dusp5 and PHLPP-1, specific phosphatases for ERK and Akt, respectively, also undergo mitochondrial translocation under oxidative stress.
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