Hepatitis C virus-core and non structural proteins lead to different effects on cellular antioxidant defenses

Maher Y. Abdalla, Iman M. Ahmad, Douglas R. Spitz, Warren N. Schmidt, Bradley E. Britigan

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

Chronic hepatitis C virus (HCV) infection leads to increased oxidative stress in the liver. Hepatic antioxidant 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)-chloromethyl-2′,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 antioxidant enzymatic responses were different. Over-expression of HCV-NS proteins increased antioxidant 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 antioxidant 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.

Original languageEnglish (US)
Pages (from-to)489-497
Number of pages9
JournalJournal of Medical Virology
Volume76
Issue number4
DOIs
StatePublished - Aug 1 2005

Fingerprint

Hepacivirus
Antioxidants
Hepatocytes
Proteins
Oxidative Stress
Virus Diseases
Liver
Enzymes
Cell Line
Thioredoxins
Heme Oxygenase-1
Chronic Hepatitis C
Oxidants
Catalase
Glutathione
Fluorescence
Wounds and Injuries
Hepatitis C virus nucleocapsid protein

Keywords

  • Hepatitis C
  • Hepatitis C core protein
  • Hepatitis C nonstructural proteins
  • Oxidative stress

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Hepatitis C virus-core and non structural proteins lead to different effects on cellular antioxidant defenses. / Abdalla, Maher Y.; Ahmad, Iman M.; Spitz, Douglas R.; Schmidt, Warren N.; Britigan, Bradley E.

In: Journal of Medical Virology, Vol. 76, No. 4, 01.08.2005, p. 489-497.

Research output: Contribution to journalArticle

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