Intracellular oxidation reduction status in the regulation of transcription factors NF-kappa B and AP-1

The eukaryotic cell contains a multitude of pathways coupling environmental stimuli to the specific regulation of gene expression. Two early response transcriptional complexes, NF-kappa B and A9-1, appear to respond to enviro nmental stressors by inducing the expression of response specific downstrea m genes. Both are well-characterized transcriptional regulatory factors tha t are induced by a wide variety of seemingly unrelated exogenous and endoge nous agents and serve important roles in cell growth and differentiation, i mmunity, inflammation, and other preprogrammed cellular genetic processes. The activities of NF-kappa B and AP-1 are also affected following exposure to chemicals, drugs, or other agents that appear to alter the cellular oxid ation/reduction (redox) status. From these observations, it has been sugges ted that changes in cellular oxidation/reduction status, communicated via a series of cellular redox-sensitive signaling circuitry employing metal- an d thiol-containing proteins, serve as common mechanisms linking environment al stressors to adaptive cellular responses. As such, these transcription f actors are ideal paradigms to study the mechanism and possible physiologica l significance of early response genes in the cellular response to changes in cellular redox status. In this article we summarize the evidence suggest ing that cellular redox regulates these transcription factors. (C) 1999 Els evier Science Ireland Ltd. All rights reserved.