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- PEROXYNITRITE HEADLINE NEWS
My research deals with peroxynitrite, a cytotoxic product of nitric oxide (NO).
- by Giuseppe L. Squadrito
"The identification of nitric oxide (NO) as the endothelium-derived relaxing factor prompted an enormous research effort to further elucidate the chemistry of this novel, gaseous messenger molecule. It is now evident that the biological effects of NO are not limited to vascular relaxation, but that they are also important in the respiratory, urogenital and gastrointestinal systems, central and peripheral nervous systems, neuroendocrine and endocrine systems, and nonspecific immunity. "
A variety of pathologies are associated with the formation of peroxynitrite, a potent oxidant formed from the reaction of NO with superoxide. This reaction is the fastest reaction NO is known to undergo, and transforms two relatively unreactive radicals into a more reactive oxidant, peroxynitrite. Peroxynitrite is invariably formed in larger amounts when more NO is produced, and/or when an elevated level of O2.- prevails. In this regard, pathologies such as diabetes, atherosclerosis, and ischemia-reperfusion injury, are associated with oxidative stress characterized by an elevated level of O2.- that can lead to increased peroxynitrite formation. Recent evidence also suggests multiple sclerosis and Alzheimer's disease are associated with peroxynitrite formation. In addition, peroxynitrite has also been implicated during ischemia and reperfusion, and during sepsis and adult respiratory distress syndrome. Ischemia and reperfusion are accompanied by an increase in superoxide due to the activation of xanthine oxidase and NAPDH oxidase, respectively. Thus, peroxynitrite is likely to be implicated in a number of pathologies in which an imbalance of NO and O2.- occurs. [The formation of peroxynitrite is desirable for non-specific immunity but possibly not during signaling by NO.]
Peroxynitrite is formed in biology from the reaction of nitric oxide and superoxide. The enzyme Superoxide Dismutase (SOD) lowers superoxide and prevents peroxynitrite formation (see my review: Pryor, W.A. and Squadrito, G.L. (1995). Am. J. Physiol. (Lung Cell. Mol. Physiol. 12) 268, L699-L722). The chemistry of peroxynitrite: a product from the reaction of nitric oxide with superoxide). Peroxynitrite is a potent oxidant and itself can oxidize many biomolecules. Nevertheless, in biological systems, it reacts mostly with carbon dioxide to form reactive intermediates, such as ONOOCO2-, O2NOCO2-, CO3.-, and .NO2. Of these intermediates, only CO3.- and .NO2 participate in bimolecular reactions with biological target molecules; the CO2 adducts ONOOCO2- and O2NOCO2- are too short-lived and decompose before they can react bimolecularly. The corresponding reactions are shown in the cycle below, as determined by Squadrito and Pryor.
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