Nitric oxide, oxidants, and protein tyrosine nitration

被引:1185
作者
Radi, R
机构
[1] Univ Republica, Fac Med, Dept Bioquim, Montevideo 11800, Uruguay
[2] Univ Republica, Fac Med, Ctr Free Rad & Biomed Res, Montevideo 11800, Uruguay
关键词
D O I
10.1073/pnas.0307446101
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The occurrence of protein tyrosine nitration under disease conditions is now firmly established and represents a shift from the signal transducing physiological actions of .NO to oxidative and potentially pathogenic pathways. Tyrosine nitration is mediated by reactive nitrogen species such as peroxynitrite anion (ONOO-) and nitrogen dioxide (.NO2), formed as secondary products of .NO metabolism in the presence of oxidants including superoxide radicals (O-2(.-)), hydrogen peroxide (H2O2), and transition metal centers. The precise interplay between .NO and oxidants and the identification of the proximal intermediate(s) responsible for nitration in vivo have been under controversy. Despite the capacity of peroxynitrite to mediate tyrosine nitration in vitro, its role on nitration in vivo has been questioned, and alternative pathways, including the nitrite/H2O2/hemeperoxidase and transition metal-dependent mechanisms, have been proposed. A balanced analysis of existing evidence indicates that (i) different nitration pathways can contribute to tyrosine nitration in vivo, and (it) most, if not all, nitration pathways involve free radical biochemistry with carbonate radicals (CO3.-) and/or oxo-metal complexes oxidizing tyrosine to tyrosyl radical followed by the diffusion-controlled reaction with .NO2 to yield 3-nitrotyrosine. Although protein tyrosine nitration is a low-yield process in vivo, 3-nitrotyrosine has been revealed as a relevant biomarker of .NO-dependent oxidative stress; additionally, site-specific nitration focused on particular protein tyrosines may result in modification of function and promote a biological effect. Tissue distribution and quantitation of protein 3-nitrotyrosine, recognition of the predominant nitration pathways and individual identification of nitrated proteins in disease states open new avenues for the understanding and treatment of human pathologies.
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页码:4003 / 4008
页数:6
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