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.
Miyazaki
Y
Y
Second Department of Internal Medicine, Osaka University Medical School, Japan.
Shinomura
Y
Y
Tsutsui
S
S
Yasunaga
Y
Y
Zushi
S
S
Higashiyama
S
S
Taniguchi
N
N
Matsuzawa
Y
Y
D000111:Acetylcysteine / Q000494:pharmacology; D066258:Amphiregulin; D000818:Animals; D002460:Cell Line; D066255:EGF Family of Proteins; D004815:Epidermal Growth Factor / Q000235:genetics*; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006023:Glycoproteins / Q000235:genetics*; D006133:Growth Substances / Q000235:genetics*; D066257:Heparin-binding EGF-like Growth Factor; D006861:Hydrogen Peroxide / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D018384:Oxidative Stress; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats
D066258:Amphiregulin; C587850:Areg protein, rat; D066255:EGF Family of Proteins; D006023:Glycoproteins; D006133:Growth Substances; C587885:Hbegf protein, rat; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D004815:Epidermal Growth Factor; D006861:Hydrogen Peroxide; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D000111:Acetylcysteine