Role of oxidants and antioxidants in the induction of AP-1, NF-kappaB, and glutathione S-transferase gene expression
| Autor: | Lev Weiner, Ron Pinkus, Violet Daniel |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Antioxidant
Pyrrolidines medicine.medical_treatment Molecular Sequence Data Butylated Hydroxyanisole Gene Expression medicine.disease_cause Biochemistry Antioxidants Cell Line chemistry.chemical_compound Pyrrolidine dithiocarbamate Thiocarbamates medicine Animals Humans Sulfhydryl Compounds Molecular Biology Glutathione Transferase biology Base Sequence NF-kappa B Cell Biology Glutathione Catalase Oxidants Acetylcysteine Hydroquinones Rats Transcription Factor AP-1 Oxidative Stress Glutathione S-transferase chemistry Oligodeoxyribonucleotides biology.protein Butylated hydroxyanisole Reactive Oxygen Species Oxidative stress Cysteine |
| Zdroj: | The Journal of biological chemistry. 271(23) |
| ISSN: | 0021-9258 |
| Popis: | Transcription factors AP-1 and NF-kappaB have been implicated in the inducible expression of a variety of genes in response to oxidative stress. Recently, based on the observation that butylated hydroxyanisole (BHA) and pyrrolidine dithiocarbamate (PDTC) induce AP-1 binding activity and AP-1-dependent gene expression and assuming that these compounds exert an antioxidant effect, it was claimed that AP-1 is an antioxidant-responsive factor. To determine whether AP-1 can be responsive to both oxidant and antioxidant, we examined the nature of BHA and PDTC inducing activity. Using EPR spectroscopy to detect semiquinone radicals, we demonstrate the autoxidation of BHA metabolite tert-butylhydroquinone (TBHQ) to tert-butylquinone. The kinetics of TBHQ-mediated generation of .OH radicals were monitored in intact hepatoma HepG2 cells by EPR spin trapping technique. Exogenous catalase inhibited the rate and amount of .OH radical formation and the induction of AP-1-mediated glutathione S-transferase (GST) Ya gene expression by BHA and TBHQ, thus indicating the intermediate formation of H2O2 in the metabolism of these chemicals. Furthermore, we show that the induction of AP-1 and NF-kappaB activities and GST Ya gene expression by BHA and TBHQ is due to a pro-oxidant activity, since this induction was inhibited by thiol compounds N-acetyl cysteine and GSH. Similarly, induction of AP-1 and GST Ya gene expression by PDTC was inhibited by N-acetyl cysteine and GSH. The present findings do not support the notion that the induction of AP-1 by BHA, TBHQ, or PDTC is an antioxidant response and demonstrate that both AP-1 and NF-kappaB activities are induced by oxygen radicals. |
| Databáze: | OpenAIRE |
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