Down-regulation of heme oxygenase-1 by hepatitis C virus infection in vivo and by the in vitro expression of hepatitis C core protein.
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.
Department of Internal Medicine and Research Service, Veterans Administration Medical Center, Roy G. and Lucille A. Carver College of Medicine, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242, USA.
Maher Y
MY
Abdalla
Bradley E
BE
Britigan
Feng
F
Wen
Michael
M
Icardi
Michael L
ML
McCormick
Douglas R
DR
LaBrecque
Michael
M
Voigt
Kyle E
KE
Brown
Warren N
WN
Schmidt
D001706:Biopsy; D015153:Blotting, Western; D002374:Catalase / Q000032:analysis; D002460:Cell Line; D015536:Down-Regulation / Q000235:genetics / Q000502:physiology*; D006419:Heme Oxygenase (Decyclizing) / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D051547:Heme Oxygenase-1; D016174:Hepacivirus / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008565:Membrane Proteins; D012313:RNA / Q000032:analysis / Q000302:isolation & purification; D012333:RNA, Messenger / Q000032:analysis / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000032:analysis; D014758:Viral Core Proteins / Q000378:metabolism*
D008565:Membrane Proteins; D012333:RNA, Messenger; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D012313:RNA; D002374:Catalase; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase