期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 130, 期 -, 页码 369-378出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2018.10.451
关键词
Peroxynitrite; Peroxiredoxin; Tyrosine nitration; Mitochondria; Sulfenic acid; Kinetics
资金
- Espacio Interdisciplinario
- Comision Sectorial de Investigacion Cientifica, Universidad de la Republica, Uruguay (CSIC I + D)
- Comision Sectorial de Investigacion Cientifica, Universidad de la Republica, Uruguay (CSIC Grupos)
- Comision Academica de Postgrado, Universidad de la Republica, Uruguay
- Programa de Desarrollo de Ciencias Basicas (PEDECIBA), Uruguay
Mitochondria are main sites of peroxynitrite formation. While at low concentrations mitochondrial peroxynitrite has been associated with redox signaling actions, increased levels can disrupt mitochondrial homeostasis and lead to pathology. Peroxiredoxin 3 is exclusively located in mitochondria, where it has been previously shown to play a major role in hydrogen peroxide reduction. In turn, reduction of peroxynitrite by peroxiredoxin 3 has been inferred from its protective actions against tyrosine nitration and neurotoxicity in animal models, but was not experimentally addressed so far. Herein, we demonstrate the human peroxiredoxin 3 reduces peroxynitrite with a rate constant of 1x10(7) M-1 s(-1) at pH 7.8 and 25 degrees C. Reaction with hydroperoxides caused biphasic changes in the intrinsic fluorescence of peroxiredoxin 3: the first phase corresponded to the peroxidatic cysteine oxidation to sulfenic acid. Peroxynitrite in excess led to peroxiredoxin 3 hyperoxidation and tyrosine nitration, oxidative post-translational modifications that had been previously identified in vivo. A significant fraction of the oxidant is expected to react with CO2 and generate secondary radicals, which participate in further oxidation and nitration reactions, particularly under metabolic conditions of active oxidative decarboxylations or increased hydroperoxide formation. Our results indicate that both peroxiredoxin 3 and 5 should be regarded as main targets for peroxynitrite in mitochondria.
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