2012 Fiscal Year Final Research Report
Association of between HCV induced mitochondria dysfunction and viral response by interferon in hepatic iron overloaded
| Project/Area Number |
22590750
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Research Institute, International Medical Center of Japan (2011-2012)
Kawasaki Medical School (2010) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
HINO Keisuke (80228741)
KORENAGA Keiko (60420535)
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| Project Period (FY) |
2010 – 2012
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| Keywords | ミトコンドリア / 鉄過剰状態 / 肝発癌 / 酸化ストレス / MAVS / IFN |
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| Research Abstract |
We previously reported that HCC developed through the oxidative stress in iron-overloaded transgenic mice expressing the hepatitis C virus (HCV) polyprotein (HCV TgM) (Gastroenterology;130: 2006) Oxidative stress is one of the pathophysiologic mechanisms involved in HCV-associated liver injury and hepatocarcinogenesis. The aim of this study was to clarify whether iron-induced oxidative stress affects HCV replication in full genomic HCV replicon cells. Methods: Various concentration of Fe(II)SO4, Fe(III)(NO3)3, FeCl2, FeCl3, Holo-transferrin apo-transferring or IFNα was added to the genome length HCV-RNA replicon (OR6) cells. Using reporter assay system, HCV replication was assessed. We also measured cellular reactive oxygen sepsis (ROS) production by DCF assay and the expression levels of HCV core protein by western blot. Result：Ferrous and ferric ions significantly inhibited HCV replication and the levels of core protein at the concentration of iron less than 1uM. However, only ferrous ions increased ROS production, suggesting that ferric ions may have inhibited HCV replication through its cytotoxicity Additional IFN treatment showed additive inhibition of HCV replication. Conclusion: Although iron- induced oxidative stress accelerates hepatocarcinogenesis, it may work as an anti-HCV factor in patients with chronic hepatitis C. These data suggested that we should avoid touse antioxidant agents during IFN therapy.
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[Presentation] Anti-interferon-α neutralizing antibodies interact with viral responses to interferon in patients with hepatitis C virus infection bearing interferon sensitive IL28B single nucleotide polymorphisms.2012
Author(s)
Korenaga M, Korenaga K, Nishina S, Yoshioka N, Tomiyama Y, Hara Y, Sugiyama M, Nishida N, Murata K, Masaki N, Mizokami M, Hino K.
Organizer
The 63rd annual meeting of the American association for the study of liver diseases (AASLD)
Place of Presentation
Boston, U.S.
Year and Date
20121100
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