Human hepatitis B virus X protein (HBx) is associated with the induction of oxidative stress, which is considered significant in the development of liver damage. In this study, we investigated the molecular mechanisms by which HBx induced lipid peroxidation and tumor necrosis factor-α (TNF-α) expression through regulation of selenoprotein P (SeP) expression in the human hepatoma cell line, HepG2. Forced expression of HBx significantly down-regulated the expression of SeP mRNA and protein in both the cell lysates and the culture medium. Lipid peroxidation increased 2.5-fold when expression of the SeP protein was blocked with a SeP antisense vector. Also, HBx transfection increased lipid peroxidation by 3.0-fold, whereas the hepatitis B virus core protein (HBc) had no significant effects. The induction of lipid peroxidation due to the block in SeP protein expression or treatment with ferric chloride (FeCl3) up-regulated the expression levels of TNF-α mRNA and protein. The pattern of HBx-induced lipid peroxidation and TNF-α up-regulation was reversed by SeP introduction. These results suggest that HBx induces lipid peroxidation via down-regulation of SeP expression, resulting in increased expression of TNF-α in the human hepatoma cell line, HepG2.
|Number of pages||8|
|Journal||Biochimica et Biophysica Acta - Molecular Basis of Disease|
|Publication status||Published - 2003 Jul 30|
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Molecular Biology