Restoration of mitophagy as a strategy for inhibiting hepatocarcinogenesis
Project/Area Number |
25670374
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Gastroenterology
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Research Institution | Kawasaki Medical School |
Principal Investigator |
HINO Keisuke 川崎医科大学, 医学部, 教授 (80228741)
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Co-Investigator(Kenkyū-buntansha) |
HARA Yuichi 川崎医科大学, 医学部, 講師 (60550952)
NISHINA Sohji 川崎医科大学, 医学部, 講師 (70550961)
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Project Period (FY) |
2013-04-01 – 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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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Keywords | 酸化ストレス / ミトコンドリア / 活性酸素種 / 鉄 / C型肝炎ウイルス / マイトファジー / C型肝炎ウイルス / mitophagy / Parkin / autophagy |
Outline of Final Research Achievements |
Oxidative stress is amplified through the suppression of mitophagy by hepatitis C virus (HCV) and plays an important role in hepatocarcinogenesis. In the present study we investigated whether iron chelation could restore mitophagy supressed by HCV. Iron chelator, deferiprone (DFP) increased LC3-II expression and mitophagosomes in HCV-infected cells. DFP also decreased mitochondrial membrane potential and reactive oxygen species (ROS) production, but not ATP production. In addition, DFP decreased mitochondrial ferrous iron content in dose dependent manner regardless of HCV infection. These results indicated that iron chelation restores mitophagy suppressed by HCV. The mechanisms underlying mitophagy induced by iron chelation remains to be unknown, but decrease in mitochondrial ferrous iron and disrupted mitochondrial function may be critical for inducing mitophagy.
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Report
(3 results)
Research Products
(23 results)
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[Journal Article] Hepatitis C virus core protein suppresses mitophagy by interacting with parkin in the context of mitochondrial depolarization.2014
Author(s)
Hara Y, Yanatori I, Ikeda M, Kiyokage E, Nishina S, Tomiyama Y, Toida K, Kishi F, Kato N, Imamura M, Chayama K, Hino K.
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Journal Title
Am J Pathol. 2014
Volume: 184
Issue: 11
Pages: 3026-39
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] New susceptibility and resistance HLA-DP alleles to HBV-related diseases identified by a trans-ethnic association study in Asia.2014
Author(s)
Nishida N, Sawai H, Kashiwase K, Minami M, Sugiyama M, Tanak Y, Kurosaki M, Asahina Y, Izumi N, Orito E, Hiasa Y, Honda M, Kaneko S, Mita E, Suzuki K, Hino K, Tanaka E, Mochida S, Mawatari Y, Ohashi J, Kawashima M, Tokunaga K, Mizokami, et al M
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Journal Title
Related Report
Peer Reviewed
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[Journal Article] Clinical usefulness of non-protein respiratory quotient measurement in non-alcoholic fatty liver disease2013
Author(s)
Korenaga K1, Korenaga M, Teramoto F, Suzuki T, Nishina S, Sasaki K, Nakashima Y, Tomiyama Y, Yoshioka N, Hara Y, Moriya T, Hino K.
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Journal Title
Hepatol Res.
Volume: 43
Issue: 12
Pages: 1284-1294
DOI
Related Report
Peer Reviewed
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[Journal Article] Treatment of nonalcoholic steatohepatitis with vitamins E and C: a pilot study2013
Author(s)
Kawanaka M, Nishino K, Suehiro M, Goto D, Urata N, Oka T, Kawamoto H, Nakamura H, Yodoi J, Hino K, Yamada G
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Journal Title
Hepatic Medicine: Evidence and Research
Volume: 5
Pages: 11-16
Related Report
Peer Reviewed
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[Presentation] Hepatitis C virus core protein suppresses mitophagy by interacting with Parkin in the context of mitochondrial depolarization2014
Author(s)
Hara Y, Yanatori I, Ikeda M, Kiyokage E, Nishina S, Tomiyama Y, Toida K, Kishi F, Kato N, Imamura M, Chayama K, Hino K
Organizer
5th World Congress on Targeting Mitochondria
Place of Presentation
Ritz Carlton Hotel, Berlin, Germany
Year and Date
2014-10-30
Related Report
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[Presentation] The hepatitis C virus core protein suppresses mitophagy by affecting Parkin
Author(s)
Yuichi Hara, Izumi Yanatori , Masanori Ikeda, Sohji Nishina, Yasuyuki Tomiyama, Fumio Kishi, Kazunori Toida, Nobuyuki Kato, Kazuaki Chayama , Keisuke Hino
Organizer
Cell Sumposium Mitochondria:from Signaling to Disease
Place of Presentation
Sheraton Lisbosa, Lisbon, Portugal
Related Report
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[Presentation] Hepatitis C virus core protein suppresses mitophagy by interacting with Parkin
Author(s)
Yuhichi Hara, Izumi Yanatori, EmiKiyokage, Sohji Nishina, Yasuyuki Tomiyama, Kazunori Toida, Masanori Ikeda, Fumio Kishi, Nobuyuki Kato, Keisuke Hino
Organizer
The 64th Annual Meeting of the American Association for the Study of Liver Diseases
Place of Presentation
Waltere Washington Convention Center, Washington DC, USA
Related Report
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