Signal transduction by nitric oxide in cellular stress responses.
Nitric oxide (NO) has received wide attention as a biological signaling molecule that uses cyclic GMP as a cellular second messenger. Other work has supported roles for cysteine oxidation or nitrosylation as signaling events. Recent studies in bacteria and mammalian cells now point to the existence of at least two other pathways independent of cGMP. For the E. coli SoxR protein, signaling occurs by nitrosylation of its binuclear iron-sulfur clusters, a reaction that is unprecedented in gene activation. In intact cells, these nitrosylated centers are very rapidly replaced by unmodified iron-sulfur clusters, a result that points to the existence of an active repair pathway for this type of protein damage. Exposure of mammalian cells to NO elicits an adaptive resistance that confers elevated resistance of the cells to higher levels of NO. This resistance in many cell types involves the important defense protein heme oxygenase 1, although the mechanism by which this enzyme mediates NO resistance remains unknown. Induction of heme oxygenase in some cell types occurs through the stabilization of its mRNA. NO-induced stabilization of mRNA is mediated by pre-existing proteins and points to the existence of an important new signaling pathway that counteracts the damage and stress exerted by this free radical.
Demple
Bruce
B
Department of Cancer Cell Biology, Harvard School of Public Health, Boston, MA 02115, USA. bdemple@hsph.harvard.edu
D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D002477:Cells / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism
D001426:Bacterial Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C070724:SoxR protein, Bacteria; D009569:Nitric Oxide; D006419:Heme Oxygenase (Decyclizing)