期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 89, 期 -, 页码 1049-1056出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2015.10.424
关键词
Peroxynitrite; Selenium; Selenols; Protein oxidation; Antioxidants; Inflammation
资金
- Australian Research Council [CE0561607, DP0988311]
- National Heart Foundation of Australia [G0954313, G11S 5811]
- Novo Nordisk Foundation [NNF130C0004294]
- Novo Nordisk Fonden [NNF13OC0004294] Funding Source: researchfish
Peroxynitrite (the physiological mixture of ONOOH and its anion, ONOO-) is a powerful biologically-relevant oxidant capable of oxidizing and damaging a range of important targets including sulfides, thiols, lipids, proteins, carbohydrates and nucleic acids. Excessive production of peroxynitrite is associated with several human pathologies including cardiovascular disease, ischemic-reperfusion injury, circulatory shock, inflammation and neurodegeneration. This study demonstrates that low-molecularmass selenols (RSeH), selenides (RSeR') and to a lesser extent diselenides (RSeSeR') react with peroxynitrite with high rate constants. Low molecular mass selenols react particularly rapidly with peroxynitrite, with second order rate constants k(2) in the range 5.1 x 10(5)-1.9 x 10(6) M-1 s(-1), and 250-830 fold faster than the corresponding thiols (RSH) and many other endogenous biological targets. Reactions of peroxynitrite with selenides, including selenosugars are approximately 15-fold faster than their sulfur homologs with k(2) approximately 2.5 x 10(3) M-1 s(-1). The rate constants for diselenides and sulfides were slower with k(2) 0.72-1.3 x 10(3) M-1 s(-1) and approximately 2.1 x 10(2) M-1 s(-1) respectively. These studies demonstrate that both endogenous and exogenous selenium-containing compounds may modulate peroxynitrite-mediated damage at sites of acute and chronic inflammation, with this being of particular relevance at extracellular sites where the thiol pool is limited. (C) 2015 Elsevier Inc. All rights reserved.
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