title: Oxidative stress and hepatic Nox proteins in chronic hepatitis C and hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) is the most common liver cancer and a leading cause of cancer-related mortality in the world. Hepatitis C virus (HCV) is a major etiologic agent of HCC. A majority of HCV infections lead to chronic infection that can progress to cirrhosis and, eventually, HCC and liver failure. A common pathogenic feature present in HCV infection, and other conditions leading to HCC, is oxidative stress. HCV directly increases superoxide and H2O2 formation in hepatocytes by elevating Nox protein expression and sensitizing mitochondria to reactive oxygen species generation while decreasing glutathione. Nitric oxide synthesis and hepatic iron are also elevated. Furthermore, activation of phagocytic NADPH oxidase (Nox) 2 of host immune cells is likely to exacerbate oxidative stress in HCV-infected patients. Key mechanisms of HCC include genome instability, epigenetic regulation, inflammation with chronic tissue injury and sustained cell proliferation, and modulation of cell growth and death. Oxidative stress, or Nox proteins, plays various roles in these mechanisms. Nox proteins also function in hepatic fibrosis, which commonly precedes HCC, and Nox4 elevation by HCV is mediated by transforming growth factor β. This review summarizes mechanisms of oncogenesis by HCV, highlighting the roles of oxidative stress and hepatic Nox enzymes in HCC.
authors.affiliation: School of Natural Sciences, University of California at Merced, Merced, CA 95343, USA. Electronic address: jchoi@ucmerced.edu.
authors.forename: Jinah
authors.initials: J
authors.lastname: Choi
authors.affiliation: School of Natural Sciences, University of California at Merced, Merced, CA 95343, USA.
authors.forename: Nicole L B
authors.initials: NL
authors.lastname: Corder
authors.affiliation: School of Natural Sciences, University of California at Merced, Merced, CA 95343, USA.
authors.forename: Bhargav
authors.initials: B
authors.lastname: Koduru
authors.affiliation: School of Natural Sciences, University of California at Merced, Merced, CA 95343, USA.
authors.forename: Yiyan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*
chemical_list: D019255:NADPH Oxidases
keywords: Cancer; Free radicals; HCV; Inflammation; NADPH oxidase; Reactive oxygen species