Development of novel therapeutic strategy for ischemic heart diseases through targeting protein degradation
| Project/Area Number |
17K09577
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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 | Osaka University |
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Principal Investigator |
Kato Hisakazu 大阪大学, 医学系研究科, 助教 (30589312)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 虚血性心疾患 / ATP / ミトコンドリア / タンパク質分解 / 薬剤スクリーニング / 心不全 / スクリーニング / 分子心臓学 |
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| Outline of Final Research Achievements |
In this study, with the aim of developing a novel therapeutic strategy for ischemic heart disease that directly enhances mitochondrial ATP production, we identified compounds that inhibit the degradation of the ATP-synthesis regulator G0S2 using originally constructed screening system. These compounds enhanced ATP production in cardiomyocytes and showed a remarkable cytoprotective effect. By further utilizing this screening system, we identified a novel E3 ligase involved in G0S2 degradation and clarified a novel mechanism of G0S2 degradation. In the future, we plan to address the mechanism of inhibiting G0S2 degradation by these compounds and to administer it to the heart failure model mice.
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| Academic Significance and Societal Importance of the Research Achievements |
心臓は持続的な収縮弛緩の繰り返しによって莫大なエネルギー（ATP）を消費する。そのため狭心症などで、ATPの需要と供給のバランスが崩れると、容易に心不全となりうる。循環器領域で幾つかの分子標的治療が進められているが、虚血性疾患を標的としたものは未だ開発されておらず、直接的にATP産生を増強させる治療法の開発が望まれている。本研究で明らかにしたATP産生制御因子G0S2の分解を阻害する化合物は、直接的に心筋細胞のATPを増産できる点において、画期的な虚血性心疾患の治療法につながることが期待される。
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Report
(4 results)
Research Products
(12 results)
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[Journal Article] Mutant KCNJ3 and KCNJ5 potassium channels as novel molecular targets in bradyarrhythmias and atrial fibrillation.2019
Author(s)
Yamada N, Asano Y, Fujita M, Yamazaki S, Inanobe A, Matsuura N, Kobayashi H, Ohno S, Ebana Y, Tsukamoto O, Ishino S, Takuwa A, Kioka H, Yamashita T, Hashimoto N, Zankov DP, Shimizu A, Asakura M, Asanuma H, Kato H, Nishida Y, Miyashita Y, Shinomiya H, Naiki N, Hayashi K, Makiyama T, Ogita H, et al.
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Journal Title
Circulation
Volume: In press
Issue: 18
Pages: 2157-2169
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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