Implications of inducible nitric oxide synthase expression and enzyme activity.
We summarize here our current knowledge about inducible nitric oxide synthase (NOS) activity in human diseases and disorders. As basic research discovers more and more effects of low or high concentrations of NO toward molecular and cellular targets, successful therapies involving inhibition of NO synthesis or application of NO to treat human diseases are still lacking. This is in part due to the fact that the impact of NO on cell function or death are complex and often even appear to be contradictory. NO may be cytotoxic but may also protect cells from a toxic insult; it is apoptosis-inducing but also exhibits prominent anti-apoptotic activity. NO is an antioxidant but may also compromise the cellular redox state via oxidation of thiols like glutathione. NO may activate specific signal transduction pathways but is also reported to inhibit exactly these, and NO may activate or inhibit gene transcription. The situation may even be more complicated, because NO, depending on its concentration, may react with oxygen or the superoxide anion radical to yield reactive species with a much broader chemical reaction spectrum than NO itself. Thus, the action of NO during inflammatory reactions has to be considered in the context of timing and duration of its synthesis as well as stages and specific events in inflammation.
Research Group Immunobiology in the Biomedical Research Centre, Heinrich-Heine-University, Düsseldorf, Germany. kroencke@uni-duesseldorf.de
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D017209:Apoptosis; D006801:Humans; D007249:Inflammation / Q000201:enzymology*; D008954:Models, Biological; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000737:chemistry; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D015398:Signal Transduction; D014158:Transcription, Genetic
D009566:Nitrates; C039642:peroxynitric acid; D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II