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 (110-1) gene expre ssion by a glutathione (GSH) depletor, phorone, is inhibited by cycloh eximide pretreatment and involves changes in c-jun, not c-fos, mRNA. B uthionine sulfoximine (BSO) enhanced markedly both c-jun and HO-1 gene expression evoked by phorone. Phorone dramatically increased AP-1 bin ding activity, which was blocked by unlabeled AP-1 oligonucleotide and abolished by anti-Jun antibodies, but not anti-Fos antibodies, in add ition, pretreatment with dexamethasone, an inhibitor of AP-1 DNA bindi ng, inhibited phorone-mediated HO-1 mRNA induction. These findings sug gest that HO-1 induction by phorone is likely to involve in the activa tion of AP-1(Jun/Jun) binding, which could be associating with GSH dep letion. (C) 1996 Academic Press, Inc.