Inducible nitric oxide synthase-derived nitric oxide in gene regulation, cell death and cell survival

Studies from many laboratories have demonstrated the complex role of NO in inflammatory processes. Prolonged exposure to NO shifts the cellular redox potential to a more oxidized state and this is critically regulated by intr acellular levels of reduced glutathione. NO-mediated stress will alter gene expression patterns, and the number of genes known to be involved is stead ily increasing. Indeed, due to its S-nitrosating activity in the presence o f oxygen, NO can modify the activity of transcription factors containing zi nc finger motifs or cysteines within the DNA-binding domain. In addition, w e are faced with not only NO acting as a powerful inducer of apoptosis or o f necrosis in some cells, but also representing an equally powerful protect ion from cell death in many instances. Some of these apparent discrepancies may be explained by different capacities of cells to cope with the stress of NO exposure. Here, we review our findings on the complex impact of NO on transcriptional regulation of genes, cell death and cell survival. These N O-mediated actions will contribute to a better understanding of the impact of inducible nitric oxide synthase (iNOS) enzyme activity during inflammato ry reactions. (C) 2001 Elsevier Science B.V. All rights reserved.