| Project/Area Number |
24659377
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Gastroenterology
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| Research Institution | Kawasaki Medical School |
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Principal Investigator |
HARA Yuichi 川崎医科大学, 医学部, 講師 (60550952)
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| Co-Investigator(Kenkyū-buntansha) |
NISHINA Sohji 川崎医科大学, 医学部, 講師 (70550961)
HINO Keisuke 川崎医科大学, 医学部, 教授 (80228741)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2014: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | HCV / マイトファジー / ミトコンドリア / 肝発癌 / 酸化ストレス / Parkin / C型肝炎ウイルス / mitophagy |
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| Outline of Final Research Achievements |
Background and aim: Hepatitis C virus (HCV) causes mitochondrial injury and oxidative stress, and impaired mitochondria are selectively eliminated through autophagy-dependent degradation (mitophagy). The basis of the hypothesis that if the impaired mitochondria was not removed by mitophagy which causes further oxidative stress and promotes hepatocarcinogenesis.Results:Translocation of the Parkin to the mitochondria was impaired in the presence of HCV infection both in vitro and in vivo. Parkin associated with the HCV core protein. Furthermore, a specific interaction between the HCV core protein and an N-terminal Parkin fragment. The suppressed Parkin translocation to the mitochondria inhibited autophagic degradation. Production of ROS was reinforced after mitophagy had been inhibited by HCV. Conclusion:Through a direct interaction with Parkin, the HCV core protein suppressed mitophagy by inhibiting Parkin translocation to the mitochondria.
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