Journal article
Heme Oxygenase-1 suppresses Hepatitis C Virus replication and increases resistance of hepatocytes to oxidant injury
Hepatology (Baltimore, Md.), Vol.48(5), pp.1430-1439
11/2008
DOI: 10.1002/hep.22491
PMCID: PMC2587102
PMID: 18972446
Abstract
Oxidative injury to hepatocytes occurs as a result of HCV infection and replication. Modulation of host cell antioxidant enzymes such as heme oxygenase-1 (HO-1) may be useful therapeutically to minimize cellular injury, reduce viral replication, and attenuate liver disease. In this report, we evaluated the effects of HO-1 overexpression on HCV replication and hepatocellular injury. Full length (FL) (Con1) or Non-structural (NS) replicons (I 389 NS3-3′) were transfected with complete human HO-1 sequences or empty vector for control. Cell lines overexpressing HO-1 (2-6 fold above basal values) or empty vector were isolated and their HCV RNA synthesis, pro-oxidant levels, and resistance to oxidative injury were assessed. HO-1 overexpression decreased HCV RNA replication in both FL and NS replicons without affecting cellular growth or DNA synthesis. The attenuation of HCV replication was significantly reversed in both replicon systems with HO-1 siRNA knockdown. Both FL and NS replicons that overexpress HO-1 showed reduced prooxidant levels at baseline and increased resistance to oxidant-induced cytotoxicity. HO-1 induction with hemin also markedly decreased HCV replication in both parental FL and NS replicon cell lines. On the other hand, knock-down of HO-1 mRNA by siRNA in parental FL or NS replicons did not significantly affect HCV replication suggesting that less than basal levels of HO-1 had minimal affect on HCV replication.
Details
- Title: Subtitle
- Heme Oxygenase-1 suppresses Hepatitis C Virus replication and increases resistance of hepatocytes to oxidant injury
- Creators
- Zhaowen Zhu - Department of Internal Medicine and Research Service, Veterans Administration Medical Center, Iowa City, IA 52246Anne T Wilson - Department of Internal Medicine, Roy G. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242M. Meleah Mathis - Department of Internal Medicine and Research Service, Veterans Administration Medical Center, Iowa City, IA 52246Feng Wen - Department of Internal Medicine, Roy G. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242Kyle E Brown - Department of Internal Medicine and Research Service, Veterans Administration Medical Center, Iowa City, IA 52246Bruce A Luxon - Department of Internal Medicine, Roy G. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242Warren N Schmidt - Department of Internal Medicine and Research Service, Veterans Administration Medical Center, Iowa City, IA 52246
- Resource Type
- Journal article
- Publication Details
- Hepatology (Baltimore, Md.), Vol.48(5), pp.1430-1439
- DOI
- 10.1002/hep.22491
- PMID
- 18972446
- PMCID
- PMC2587102
- NLM abbreviation
- Hepatology
- ISSN
- 0270-9139
- eISSN
- 1527-3350
- Language
- English
- Date published
- 11/2008
- Academic Unit
- Gastroenterology and Hepatology; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984047681502771
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