H2O2 and antioxidants have opposite effects on activation of NF-kappa B and AP-1 in intact cells: AP-1 as secondary antioxidant-responsive factor.
We show that AP-1 is an antioxidant-responsive transcription factor. DNA binding and transactivation by AP-1 were induced in HeLa cells upon treatment with the antioxidants pyrrolidine dithiocarbamate (PDTC) and N-acetyl-L-cysteine (NAC), and upon transient expression of the antioxidative enzyme thioredoxin. While PDTC and NAC enhanced DNA binding and transactivation of AP-1 in response to phorbol ester, the oxidant H2O2 suppressed phorbol ester activation of the factor. H2O2 on its own was only a weak inducer of AP-1. Activation of AP-1 by PDTC was dependent on protein synthesis and involved transcriptional induction of c-jun and c-fos genes. Transcriptional activation of c-fos by PDTC was conferred by the serum response element, suggesting that serum response factor and associated proteins function as primary antioxidant-responsive transcription factors. In the same cell line, the oxidative stress-responsive transcription factor NF-kappa B behaved in a manner strikingly opposite to AP-1. DNA binding and transactivation by NF-kappa B were strongly activated by H2O2, while the antioxidants alone were ineffective. H2O2 potentiated the activation of NF-kappa B by phorbol ester, while PDTC and NAC suppressed PMA activation of the factor. PDTC did not influence protein kinase C (PKC) activity and PKC activation by PMA, indicating that the antioxidant acted downstream of and independently from PKC.[1]References
- H2O2 and antioxidants have opposite effects on activation of NF-kappa B and AP-1 in intact cells: AP-1 as secondary antioxidant-responsive factor. Meyer, M., Schreck, R., Baeuerle, P.A. EMBO J. (1993) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg
