REGULATION OF THE TRANSCRIPTION FACTORS NF-KAPPA-B AND AP-1 BY REDOX CHANGES

There is increasing evidence that reactive oxygen intermediates (ROIs) play an important role in cellular processes such as signal transduction and the control of gene expression. The activity of transcription factors like AP-1 and NF-kappa B is modulated by the redox state of the cell. NF-kappa B is activated by a prooxidant state in the cell and is therefore potentially inhibited by antioxidants. In contrast, AP-1 is strongly activated by antioxidants and shows reduced activity in the presence of oxidants. The antioxidant-mediated activation of AP-1 relies on the de novo synthesis of c-fos and c-jun mRNAs. Induction of c-fos expression is primarily mediated by transcription factors binding to the SRE element in the c-fos promoter. Thus SRE binding factors can be considered as primary antioxidant response factors, while AP-1 itself is a secondary response factor.