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.
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 humanhepatoma 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.
Authors: Vania Bonifaz; Ying Shan; Richard W Lambrecht; Susan E Donohue; Darcy Moschenross; Herbert L Bonkovsky Journal: Liver Int Date: 2008-08-07 Impact factor: 5.828
Authors: Zhaowen Zhu; Anne T Wilson; Bruce A Luxon; Kyle E Brown; M Meleah Mathahs; Sarmistha Bandyopadhyay; Anton P McCaffrey; Warren N Schmidt Journal: Hepatology Date: 2010-12 Impact factor: 17.425
Authors: Giovanni Li Volti; David Sacerdoti; Claudia Di Giacomo; Maria-Luisa Barcellona; Antonio Scacco; Paolo Murabito; Antonio Biondi; Francesco Basile; Diego Gazzolo; Raul Abella; Alessandro Frigiola; Fabio Galvano Journal: World J Gastroenterol Date: 2008-10-28 Impact factor: 5.742
Authors: Zhaowen Zhu; Anne T Wilson; M Meleah Mathahs; Feng Wen; Kyle E Brown; Bruce A Luxon; Warren N Schmidt Journal: Hepatology Date: 2008-11 Impact factor: 17.425
Authors: Alexander J Gill; Colleen E Kovacsics; Patricia J Vance; Ronald G Collman; Dennis L Kolson Journal: J Virol Date: 2015-08-12 Impact factor: 5.103
Authors: Jianyu Zheng; Ying Shan; Richard W Lambrecht; Susan E Donohue; Herbert L Bonkovsky Journal: Mol Cell Biochem Date: 2008-08-22 Impact factor: 3.396