HCV proteins increase expression of heme oxygenase-1 (HO-1) and decrease expression of Bach1 in human hepatoma cells.
OBJECTIVE
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.
Ghaziani
Tahereh
T
Department of Medicine, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-1111, USA.
Shan
Ying
Y
Lambrecht
Richard W
RW
Donohue
Susan E
SE
Pietschmann
Thomas
T
Bartenschlager
Ralf
R
Bonkovsky
Herbert L
HL
D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000821:virology; D045744:Cell Line, Tumor; D051856:Fanconi Anemia Complementation Group Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006526:Hepatitis C / Q000150:complications / Q000201:enzymology / Q000503:physiopathology*; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000821:virology; D008930:Mitochondria, Liver / Q000502:physiology; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics; D014764:Viral Proteins / Q000502:physiology*
C102108:BACH1 protein, human; D050976:Basic-Leucine Zipper Transcription Factors; D051856:Fanconi Anemia Complementation Group Proteins; D012333:RNA, Messenger; D014764:Viral Proteins; D051547:Heme Oxygenase-1