Journal article
Hepatitis C core protein inhibits induction of heme oxygenase-1 and sensitizes hepatocytes to cytotoxicity
Cell biology and toxicology, Vol.24(2), pp.175-188
04/2008
DOI: 10.1007/s10565-007-9027-9
PMID: 17721824
Abstract
Hepatitis C virus (HCV) core protein is a transcriptional modifier whose expression is associated with increased levels of prooxidants in hepatocytes in vivo and in vitro. We previously reported that HCV-infected liver biopsies and core protein-expressing hepatocytes show diminished levels of heme oxygenase-1 (HO-1), which is an important oxidative defense enzyme. The objective of these studies was to test the hypothesis that the expression of core protein sensitizes hepatocytes to toxic injury and inhibits the induction of HO-1 in response to stress. The effects of core protein were tested in two different human hepatocyte cell lines, HepG2 and Huh7, which show increased prooxidative activity and cytotoxicity after treatment with heme, heavy metals, and peroxides compared to control cells. HO-1 is upregulated in response to these treatments in control cells, while the induction is attenuated in core protein-expressing cells. The effects of core protein on HO-1 expression are not accounted for by differences in HO-1 mRNA turnover or by the known effects of core protein on cellular proliferation. Collectively, these data suggest that HCV core protein may contribute to hepatocellular injury by increasing both steady-state levels of prooxidants and the susceptibility of hepatocytes to damage by impairing their response to other sources of oxidative stress.
Details
- Title: Subtitle
- Hepatitis C core protein inhibits induction of heme oxygenase-1 and sensitizes hepatocytes to cytotoxicity
- Creators
- Feng Wen - Department of Internal Medicine Roy G. and Lucille A. Carver College of Medicine, University of Iowa Iowa City IA 52242 USAKyle Brown - Department of Internal Medicine Roy G. and Lucille A. Carver College of Medicine, University of Iowa Iowa City IA 52242 USABradley Britigan - Department of Internal Medicine University of Cincinnati College of Medicine and Veterans Administration Medical Center Cincinnati OH 45267 USAWarren Schmidt - Department of Internal Medicine University of Iowa Hospitals and Clinics 200 Hawkins Drive, 4553 JCP Iowa City IA 52242 USA
- Resource Type
- Journal article
- Publication Details
- Cell biology and toxicology, Vol.24(2), pp.175-188
- Publisher
- Springer Netherlands; Dordrecht
- DOI
- 10.1007/s10565-007-9027-9
- PMID
- 17721824
- ISSN
- 0742-2091
- eISSN
- 1573-6822
- Language
- English
- Date published
- 04/2008
- Academic Unit
- Gastroenterology and Hepatology; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984047680202771
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