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.