Background/Aims
Hepatitis C infection induces hepatic oxidative stress. Heme oxygenase (HO), the rate-controlling
enzyme of heme catabolism, plays a key role as a protector against oxidative, and
other stresses. Other recent work has implicated Bach1, a heme binding protein that
represses gene expression, in the regulation of HO-1 gene expression.
Methods
We investigated the effects of HCV polyprotein expression on expression of HO-1 and
Bach1 genes in human hepatoma cells (Huh-7 cells).
Results
HO-1 was up-regulated in the cell line expressing HCV proteins from core up to the
aminoterminal domain of NS3. Addition of increasing concentrations of N-acetylcysteine (NAC) led to down-regulation of HO-1 in cells expressing HCV proteins.
In contrast, Bach1 was significantly down-regulated in these cells. Sodium arsenite,
a strong inducer of oxidative stress and HO-1, reduced Bach1 expression in wild type
Huh-7 cells, and NAC partially abrogated this decrease.
Conclusions
Huh-7 cells expressing HCV proteins show significant up-regulation of the HO-1 gene,
and reciprocal down-regulation of the Bach1 gene. Exogenous oxidative stressors and
anti-oxidants can modulate expression of these genes. These and other results suggest
a key role of down-regulation of Bach1 and up-regulation of HO-1 in diminishing cytotoxic
effects of HCV proteins in human hepatocytes.
Keywords
Abbreviations::
AP (activator protein), ARE (anti-oxidant response element), HCV (hepatitis C virus), HO (heme oxygenase), Nrf2 (NF-E2-related factor 2), NS (nonstructural), ROS (reactive oxygen species), RT-PCR (reverse transcription-polymerase chain reaction)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: February 03, 2006
Accepted:
December 8,
2005
Received in revised form:
October 19,
2005
Received:
July 13,
2005
Identification
Copyright
© 2006 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.
