Epidermal growth factor regulation of glutathione S-transferase gene expression in the rat is mediated by class Pi glutathione S-transferase enhancer I.
Using chloramphenicol acetyltransferase assays we showed that epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha), and 3,3',4,4',5-pentachlorobiphenyl (PenCB) induce class Pi glutathione S-transferase (GSTP1) in primary cultured rat liver parenchymal cells. GSTP1 enhancer I (GPEI), which is required for the stimulation of GSTP1 expression by PenCB, also mediates EGF and TGF alpha stimulation of GSTP1 gene expression. However, hepatocyte growth factor and insulin did not stimulate GPEI-mediated gene expression. On the other hand, the antioxidant reagents butylhydroxyanisole and t-butylhydroquinone, stimulated GPEI-mediated gene expression, but the level of GSTP1 mRNA was not elevated. Our observations suggest that EGF and TGF alpha induce GSTP1 by the same signal transduction pathway as PenCB. Since the sequence of GPEI is similar to that of the antioxidant responsive element (ARE), some factors which bind to ARE might play a role in GPEI-mediated gene expression.
Matsumoto
M
M
Environmental Health Sciences Division, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba 305-0053, Japan. michi@nies.go.jp
Imagawa
M
M
Aoki
Y
Y
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001483:Base Sequence; D002083:Butylated Hydroxyanisole / Q000494:pharmacology; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism*; D004965:Estrogen Antagonists / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D017930:Genes, Reporter; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000096:biosynthesis* / Q000378:metabolism*; D006133:Growth Substances / Q000494:pharmacology; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006873:Hydroquinones / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008969:Molecular Sequence Data; D010957:Plasmids / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D014162:Transfection; D016211:Transforming Growth Factor alpha / Q000378:metabolism
D000975:Antioxidants; D004965:Estrogen Antagonists; D006133:Growth Substances; D006873:Hydroquinones; D007328:Insulin; D007527:Isoenzymes; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D002083:Butylated Hydroxyanisole; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor; C018855:2-tert-butylhydroquinone; D011078:Polychlorinated Biphenyls; D015500:Chloramphenicol O-Acetyltransferase; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C496558:Gstp1 protein, rat; C023035:3,4,5,3',4'-pentachlorobiphenyl