Peroxynitrite ONOO

Peroxynitrite (ONOO-) is a cytotoxic reactive species that is formed by the reaction of nitric oxide and superoxide. Methods for measuring the scavenging capacity of peroxynitrite usually depend on either the inhibition of tyrosine nitration or the inhibition of dihydrorhodamine 123 (DHR) oxidation to rhodamine 123 (MacDonalds-Wicks and... 

NO may react with superoxide to yield the highly reactive peroxynitrite, ONOO-. Superoxide may also be converted into H202 and the reactive hydroxyl radical, OH. In this way excessive activation of glutamate receptors leads to oxidative damage. The calcium influx has a major effect on mitochondria and causes them to depolarize and swell. This leads to a pore being formed in the outer mitochondrial membrane, which allows the escape of cytochrome c and procaspases from the mitochondria into the cytosol. Cytochrome c activates the caspase cascade, which leads to apoptotic cell death (Ch. 35). 

Other postulated routes (Jourd heuil et al., 2003) to RSNO formation include the reaction between NO and 02 to yield N02 via a second-order reaction. NO and thiolate anion, RS, react giving rise to thiyl radical, (RS ) [e]. RS then reacts with NO to yield RSNO [f]. The reaction between RS and RS- can also be the source of non-enzymatic generation of superoxide anion (02 ) [g], [h]. 02 reacts with NO to produce peroxynitrite (ONOO ) [i] (Szabo, 2003). Thiols react with ONOOH to form RSNOs [k] (van der Vliet et al.,1998). 

Pro-oxidant effects. The antioxidant effect described above occurs when NO concentrations are low. If the concentration of NO rises, rather than reducing the damaging effects of 02" the two may combine to form an even more powerful oxidant called peroxynitrite (ONOO ) ... 

Peroxynitrite (ONOO ) is a cytoxic species that is considered to form nitric oxide (NO) and superoxide (Oj ) in biological systems (Beckman et al. 1990). The toxicity of this compound is attributed to its ability to oxidize, nitrate, and hydroxylate biomolecules. Tyrosine is nitrated to form 3-nitrotyrosine (Ramazanian et al. 1996). Phenylalanine is hydroxylated to yield o-, m-, and p-tyrosines. Cysteine is oxidized to give cystine (Radi et al. 1991a). Glutathione is converted to S-nitro- or S-nitroso derivatives (Balazy et al. 1998). Catecholamines are oxidatively polymerized to melanin (Daveu et al. 1997). Lipids are also oxidized (Radi 1991b) and DNA can be scissored by peroxynitrite (Szabo and Ohshima 1997). 

Deleterious protein cross-linking can also be induced by reactive nitrogen species (RNS) such as peroxynitrite ONOO formed by the reaction of superoxide with nitric oxide (NO). The cross-links are formed between tyrosine residues following nitration by peroxynitrite (Sitte, 2003). Carnosine appears to play roles not only in NO generation but also in protection against excess NO production by inducible nitric oxide synthetase (NOS), thereby preventing ONOO-mediated protein modification (Fontana et ah, 2002). Evidence for a carnosine-NO adduct has also been published (Nicoletti et al., 2007). 

The stable free radical nitric oxide (NO) has an important role as a biological messenger. The reaction of NO with superoxide (O2 ) forms the powerful oxidant peroxynitrite (ONOO ), and a mechanism for the reaction of ONOO resulting in the abstraction of H from C—H bonds is shown (equations 109, 110). The formation of HO from the spontaneous decomposition of peroxynitrite, and of COJ radicals from CO2 catalyzed decomposition of peroxynitrite, have been demonstrated. ... 

Measurement of nitric oxide by absorption into hydrophobic tubing. The apparent disappearance of nitric oxide is due to uptake into the hydrophobic tubing and is independent of the oxygen concentration in the solution. Peroxynitrite (ONOO") rapidly destroys nitric oxide as shown by the rapid decrease in the signal. The details of the basic apparatus are shown in Fig. 18. 

NO reacts very efficiently with superoxide to form peroxynitrite (ONOO-), a highly reactive oxidant that leads to DNA damage, nitration of tyrosine, and oxidation of cysteine to disulfides or to various sulfur oxides (SOx). Several cellular... 

Among the oxygen-derived free radicals, the species of primary concern include superoxide anion (O -), hydrogen peroxide (H202), and hydroxyl radical (OH-). The superoxide is further converted in peroxynitrite (ONOO-) by reacting with nitric oxide. 

Fig. 9.2 Schematic diagram depicting the possible mechanisms by which hyperglycemia/diabetes decreases the expression of Gia proteins and adenylyl cyclase signaling. Diabetes/hyperglycemia augments the levels of vasoactive peptides including Ang II/ET-1 that enhance the oxidative stress by increasing the levels of superoxide anion (O2 ) and peroxynitrite (ONOO ). O2 and ONOO-decrease the levels of Gi proteins.The treatment with antioxidants and ONOO- scavengers reverses the hyperglycemia-induced decreased expression of Gia proteins and adenylyl cyclase signaling.

Although direct toxicity of NO- is very modest, it is significantly increased when NO- reacts with 02 to form peroxynitrite (ONOO ), a very strong oxidant. 

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