Down-Regulation of Heme Oxygenase-1 by Hepatitis C Virus Infection In Vivo and by the In Vitro Expression of Hepatitis C Core Protein

• Published in: The Journal of infectious diseases Vol. 190; no. 6; pp. 1109 - 1118
• Main Authors: Abdalla, Maher Y., Britigan, Bradley E., Wen, Feng, Icardi, Michael, McCormick, Michael L., LaBrecque, Douglas R., Voigt, Michael, Brown, Kyle E., Schmidt, Warren N.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 15.09.2004; University of Chicago Press; Oxford University Press
• Subjects: Antioxidants; Biological and medical sciences; Biopsy; Blotting, Western; Catalase - analysis; Cell Line; Cell lines; Down-Regulation - genetics; Down-Regulation - physiology; Enzymes; Fundamental and applied biological sciences. Psychology; Heme Oxygenase (Decyclizing) - analysis; Heme Oxygenase (Decyclizing) - genetics; Heme Oxygenase (Decyclizing) - immunology; Heme Oxygenase-1; Hepacivirus; Hepacivirus - metabolism; Hepacivirus - pathogenicity; Hepatitis C virus; Hepatocytes; Human viral diseases; Humans; Immunohistochemistry; Infections; Infectious diseases; Liver; Liver - enzymology; Liver - pathology; Medical sciences; Membrane Proteins; Messenger RNA; Microbiology; Oxidative stress; Reverse Transcriptase Polymerase Chain Reaction; RNA; RNA - analysis; RNA - isolation & purification; RNA, Messenger - analysis; RNA, Messenger - isolation & purification; Superoxide Dismutase - analysis; Viral Core Proteins - metabolism; Viral diseases; Viral hepatitis; Viruses; Infection; Oxygenase; Microbiology; Enzyme; Viral disease; Heme; Digestive diseases; Hepatic disease; Oxidoreductases; Protein; Viral hepatitis C
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/423488

Antioxidant enzymes, including heme oxygenase (HO)-1, are an important line of defense against oxidant-mediated liver injury. Because hepatitis C virus (HCV) infection appears to increase the production of oxidants, we evaluated levels of antioxidant enzymes and HO-1 in liver-biopsy samples from HCV-infected patients by immunoblot and semiquantitative reverse-transcriptase polymerase chain reaction. In HCV-infected liver samples, levels of immunoreactive HO-1 and HO-1 mRNA were >4-fold lower than levels in control samples, but levels of superoxide dismutase and catalase were unaffected. Immunohistochemical results confirmed the decreased expression of HO-1 in hepatocytes from liver samples from HCV-infected patients but not in those from patients with other chronic liver diseases. The expression of HO-1 was also reduced in cell lines that stably express HCV core protein, which suggests that core gene products are capable of regulating the expression of HO-1.