Peroxynitrite protein oxidation effects

Arteel and Sies (1999) examined procyanidin oligomers of different size, isolated from the seeds of Theobroma cacao, for their ability to protect against nitration of tyrosine. Serraino and others (2003) investigated antioxidant activity of the blackberry juice and cyanidin-3-O-glucoside on endothelial dysfunction in cells and in vascular rings exposed to peroxynitrite. However, more work is needed in this area, and the confounding effects of oxidized protein/amino acids in the diet need to be elucidated. 

Peroxynitrite and Nitric Oxide and Their Effects on Proteins. 201... 

Proteins, due to the complexity of their chemical structures, undergo oxidative modifications in subsequent stages which depend both on the presence of oxidation-susceptible groups and on steric availability of these groups for oxidant attacks (S25). Some oxidative structural modifications produced in proteins are common in various oxidants. Some modifications, such as chlorinated and nitrated protein derivatives produced in reactions with hypochlorite, peroxynitrite, and nitric dioxide, are specific for the oxidants employed. Certain oxidative protein modifications, such as interchain or intrachain disulfide bond formation or thiolation, are reversible and may be reduced back to the protein native form when oxidative stress is over (Dl). Other changes, such as sulfone formation, chlorination, and nitration, are irreversible and effect protein denaturation and promote its subsequent degradation. 

Peroxynitrite, like other oxidants, reacts with proteins, first oxidizing cysteine methionine and tryptophan residues (A7). The reaction products are sulfones, carbonyl moieties, and dityrosines (K23, M29). Formation of protein hydroperoxides and protein fragmentation was also observed (B7, G6). Nitric oxide induces oxidation of methionine residues, thus effecting oxidative damage to proteins (Cl 1). It also reacts with Fe-S clusters of aconitase (D15), though in most cases it is difficult to assess whether these effects are produced by the NO itself, or rather by a more reactive secondary product such as peroxynitrite (C5). At physiological... 

Gow AJ, Duran D, Malcolm S, Ischiropoulos H (1996) Effects of peroxynitrite-induced protein modifications on tyrosine phosphorylation and degradation. FEES Lett 385 63-66 Grune T, Merker K, Sandig G, Davies KJ (2003) Selective degradation of oxidatively modified protein substrates by the proteasome. Biochem Biophys Res Commun 305 709-718 Halliwell B (2002) Hypothesis proteasomal dysfunction a primary event in neurogeneration that leads to nitrative and oxidative stress and subsequent cell death. Ann N Y Acad Sci 962 182-194... 

Nitric oxide released by macrophages during inflammation reacts with active oxygen to form peroxynitrite. Peroxynitrite nitrates protein and peroxidizes lipids. y-Tocopherol (the principal form of vitamin E in the United States diet) and a-tocopherol (the major form present in the European diet and in supplements), both protect against peroxynitrite-induced lipid oxidation. [13]. Christen et al. reported that lipid hydroperoxide formation in liposomes is inhibited more effectively by y-tocopherol than a-tocopherol by a non-antioxidant mechanism [14]. However, Goss et al. [15] concluded that the presence of a-tocopherol attenuates nitration of both y-tocopherol and tyrosine, showing that nitration of... 

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