期刊
NITRIC OXIDE-BIOLOGY AND CHEMISTRY
卷 31, 期 -, 页码 20-30出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.niox.2013.03.003
关键词
Diphenyl diselenide; Endothelial cells; Apoptosis; Peroxynitrite; Intracellular glutathione; Glutathione peroxidase
资金
- Portuguese institution FCT [POCI/AGR/599919/2004]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
- Fundacao de Apoio a Pesquisa do Estado de Santa Catarina (FAPESC)
- CAPES
- Howard Hughes Medical Institute
- International Center for Genetic Engineering and Biotechnology
- CONICYT-Fondo Clemente Estable, Uruguay
Excess production of superoxide (O-2(center dot-)) and nitric oxide ((NO)-N-center dot) in blood vessel walls may occur early in atherogenesis leading to the formation of peroxynitrite, a strong oxidant and nitrating agent. This study was designed to determine the effect of diphenyl diselenide (PhSe)(2), a synthetic organoselenium compound, in comparison with ebselen, on peroxynitrite-mediated endothelial damage. Experimental results showed that pre-incubation of BAEC (24 h) with low concentrations of (PhSe)(2) (0.5 and 1 mu M) protected the cells from peroxynitrite-dependent apoptosis and protein tyrosine nitration. The intracellular levels of GSH were almost completely depleted by peroxynitrite and, although the compounds did not restore its normal levels, (PhSe)(2) per se significantly increased GSH in a concentration-dependent manner. Moreover, (PhSe)(2), which was about two times more active as a GPx mimic than ebselen, induced a significantly higher increase in both cellular GPx expression and activity. Taking into account the kinetics of the reaction between peroxynitrite and (PhSe)(2), our data indicate that (PhSe)(2) protects BAEC against peroxynitrite-mediated cell damage not by a direct reaction, but rather by increasing cellular GPx expression as a consequence of enhanced nuclear translocation of Nrf-2, which together with the increase in intracellular GSH, may work catalytically to reduce peroxynitrite to nitrite. (C) 2013 Published by Elsevier Inc.
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