Oxidative stress increases gene expression of heparin-binding EGF-like growth factor and amphiregulin in cultured rat gastric epithelial cells.

We investigated the effects of oxidative stress on mRNA levels of heparin-binding epidermal growth factor-like growth factor (HB-EGF) and amphiregulin (AR) in rat gastric epithelial RGM1 cells. In response to stimulation with hydrogen peroxide (100-400 microM), gene expression of HB-EGF and AR increased in a dose-dependent manner, peaked at 3 h, and returned to the base line at 7 h. Hydrogen peroxide-induced HB-EGF and AR gene expression was blocked by pretreatment with an antioxidant N-acetyl-cysteine. In addition, it was significantly inhibited by pretreatment with EGF receptor-specific tyrphostin AG1478, but not by depletion of protein kinase C. These data indicate that oxidative stress upregulates expression of EGF-related polypeptides and the possible involvement of EGF receptor in this process.