Heme oxygenase-1 gene expression by a glutathione depletor, phorone, mediated through AP-1 activation in rats.
This study shows that induction of heme oxygenase-1 (HO-1) gene expression by a glutathione (GSH) depletor, phorone, is inhibited by cycloheximide pretreatment and involves changes in c-jun, not c-fos, mRNA. Buthionine sulfoximine (BSO) enhanced markedly both c-jun and HO-1 gene expression evoked by phorone. Phorone dramatically increased AP-1 binding activity, which was blocked by unlabeled AP-1 oligonucleotide and abolished by anit-Jun antibodies, but not anti-Fos antibodies. In addition, pretreatment with dexamethasone, an inhibitor of AP-1 DNA binding, inhibited phorone-mediated HO-1 mRNA induction. These findings suggest that HO-1 induction by phorone is likely to involve in the activation of AP-1 (Jun/Jun) binding, which could be associating with GSH depletion.
Oguro
T
T
Department of Biochemical Toxicology, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Hayashi
M
M
Numazawa
S
S
Asakawa
K
K
Yoshida
T
T
D000818:Animals; D001483:Base Sequence; D005786:Gene Expression Regulation / Q000187:drug effects*; D005978:Glutathione / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D007659:Ketones / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D007659:Ketones; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; C018637:phorone; D006419:Heme Oxygenase (Decyclizing); D005978:Glutathione