Hepatitis C virus-induced oxidative stress and mitochondrial dysfunction: A focus on recent advances in proteomics

Authors

  • Maria Paola Simula,

    1. Experimental and Clinical Pharmacology Unit, CRO Centro di Riferimento Oncologico, IRCCS National Cancer Institute, AVIANO (PN), Italy
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  • Valli De Re

    Corresponding author
    1. Experimental and Clinical Pharmacology Unit, CRO Centro di Riferimento Oncologico, IRCCS National Cancer Institute, AVIANO (PN), Italy
    • Experimental and Clinical Pharmacology Unit, CRO Centro di Riferimento Oncologico, IRCCS National Cancer Institute, via F. Gallini 2, 33081 AVIANO (PN), Italy Fax: +39-0434-659659
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Abstract

The natural history of chronic hepatitis C virus (HCV) infection presents two major aspects. On one side, the illness is by itself benign, whereas, on the other side, epidemiological evidence clearly identifies chronic HCV infection as the principal cause of cirrhosis, hepatocellular carcinoma, and extrahepatic diseases, such as autoimmune type II mixed cryoglobulinemia and some B cell non-Hodgkin's lymphomas. The mechanisms responsible for the progression of liver disease to severe liver injury are still poorly understood. Nonetheless, considerable biological data and studies from animal models suggest that oxidative stress contributes to steatohepatitis and that the increased generation of reactive oxygen and nitrogen species, together with the decreased antioxidant defense, promotes the development of hepatic and extrahepatic complications of HCV infection. The principal mechanisms causing oxidative stress in HCV-positive subjects have only been partially elucidated and have identified chronic inflammation, iron overload, ER stress, and a direct activity of HCV proteins in increasing mitochondrial ROS production, as key events. This review summarizes current knowledge regarding mechanisms of HCV-induced oxidative stress with its long-term effects in the context of HCV-related diseases, and includes a discussion of recent contributions from proteomics studies.

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