Peroxynitrite diseases implicated

Many pathological conditions, including ischemia/reperfusion, inflammation, and sepsis may induce tissues to simultaneously produce both superoxide and nitric oxide. For example, ischemia allows intracellular calcium to accumulate in endothelium (Fig. 20). If the tissue is reperfused, the readmission of oxygen will allow nitric oxide as well as superoxide to be produced (Beckman, 1990). For each 10-fold increase in the concentration of nitric oxide and superoxide, the rate of peroxynitrite formation will increase by 100-fold. Sepsis causes the induction of a second nitric oxide synthase in many tissues, which can produce a thousand times more nitric oxide than the normal levels of the constitutive enzyme (Moncada et al., 1991). Nitric oxide and indirectly peroxynitrite have been implicated in several important disease states. Blockade of nitric oxide synthesis with N-methyl or N-nitroarginine reduces glutamate-induced neuronal degeneration in primary cortical cultures (Dawson et al., 1991). Nitroarginine also decreases cortical infarct volume by 70% in mice subjected to middle cerebral artery occlusion (Nowicki et al., 1991). Myocardial injury from a combined hy-... 

The xanthine oxidoreductases are large, complex molybdo-flavoproteins with roles in the catabolism of purines, for example, oxidizing hypoxanthine to xanthine and xanthine to uric acid (equation 9). Xanthine oxidase can also catalyze the reduction of nitrate to nitrite (or in the presence superoxide, peroxynitrite) and the reduction of nitrite to nitric oxide. Peroxynitrite, a powerfiil and destructive oxidant, has been implicated in diseases such as arthritis, atherosclerosis, multiple sclerosis, and Alzheimer s and Parkinson s diseases. The microbicidal role of milk and intestinal xanthine oxidase may also involve the generation of peroxynitrite in the gut. The high levels of the enzyme in the mammary glands of pregnant... 

The in vivo nitration of tyrosine by peroxynitrite and other reactive nitrogen species is implicated in many disease states and is an area of active research (40). It has recently been proposed that tyrosine nitration, mediated by nitric oxide and superoxide, is a regulated cell signaling pathway that provides quick response to the microenvironment of the cell (41 3). 

Vauzour D, Ravaioli G, VafeiAdou K, Rodriguez-Mateos A, Angeloni C, Spencer JP (2008) Peroxynitrite induced formation of the neurotoxins 5-S-cysteinyl-dopamine and DHBT-1 implications for Parkinson s disease and protection by polyphenols. Arch Biochem Biophys 476(2) 145-151... 

Reynolds MR, Berry RW, Binder LI. (2005) Site-specific nitration and oxidative dityrosine bridging of the tau protein by peroxynitrite implications for Alzheimer s disease. Biochemistry. 44, 1690-1700. 

---