Journal
JOURNAL OF MEDICAL VIROLOGY
Volume 76, Issue 4, Pages 489-497Publisher
WILEY
DOI: 10.1002/jmv.20388
Keywords
hepatitis C; hepatitis C core protein; hepatitis C nonstructural proteins; oxidative stress
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Funding
- NCI NIH HHS [P01-CA66081] Funding Source: Medline
- NIAAA NIH HHS [R01 AA13215-01] Funding Source: Medline
- NIAID NIH HHS [R01 AI34954] Funding Source: Medline
- NIDDK NIH HHS [R03 DK54842-03] Funding Source: Medline
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Chronic hepatitis C virus (HCV) infection leads to increased oxidative stress in the liver. Hepatic antioxiclant enzymes provide an important line of defense against oxidative injury. To understand the antioxidant responses of hepatocytes to different HCV proteins, we compared changes in antioxidative enzymes in HCV-core and HCV-nonstructural protein expressing hepatocyte cell lines. We found that expression of HCV-core protein in hepatocyte cell lines leads to increased oxidative stress as determined by increased in the oxidant-sensitive probe 5-(and-6)-chloromethyl2 ',7 '-dichlorodihydrofluorescein diacetate (CM-DCFH2) fluorescence, decreased reduced glutathione (GSH), and increased oxidation of thioredoxin (Trx). Although the expression of HCV-nonstructural (HCV-NS) proteins led to increased oxidative stress as well, the antioxiclant enzymatic responses were different. Over-expression of HCV-NS proteins increased antioxiclant enzymes (MnSOD and catalase), heme oxygenase-1 (HO-1), and GSH, indicating different mechanism(s) of prooxidative activity than HCV-core protein. Our findings show that different HCV proteins induce different antioxiclant defense responses in hepatocytes. These findings may facilitate understanding the interaction of different HCV proteins with infected liver cells and help identify possible factors contributing to hepatocyte damage during HCV infection. (c) 2005Wiley-Liss, Inc.
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