Novel therapeutic approach for heart failure by suppression of mitochondrial translocation of GSK-3beta

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461132
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Sapporo Medical University
• Principal Investigator: Tanno Masaya 札幌医科大学, 医学部, 講師 (00398322)
• Project Period (FY): 2014-04-01 – 2017-03-31
• 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

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.

Free Research Field

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