Impact of SIN-1-derived peroxynitrite flux on endothelial cell redox homeostasis and bioenergetics: protective role of diphenyl diselenide via induction of peroxiredoxins.
Increased production of reactive nitrogen (RNS) and oxygen (ROS) species and its detrimental effect to mitochondria are associated with endothelial dysfunction. This study was designed to determine the effect of a peroxynitrite flux, promoted by 1,3-morpholinosydnonimine (SIN-1), in mitochondrial function and some redox homeostasis parameters in bovine aortic endothelial cells (BAEC). Moreover, the effect of diphenyl diselenide (PhSe)2, a simple organic selenium compound, in preventing peroxynitrite-mediated cytotoxicity was also investigated. Our results showed that overnight exposure to SIN-1 (250 μM) caused a profound impairment of oxygen consumption, energy generation and reserve capacity in mitochondria of BAEC. Mitochondrial dysfunction resulted in an additional intracellular production of peroxynitrite, amplifying the phenomenon and leading to changes in redox homeostasis. Moreover, we observed an extensive decline in mitochondrial membrane potential (ΔΨm) induced by peroxynitrite and this event was associated with apoptotic-type cell death. Alternatively, the pretreatment of BAEC with (PhSe)2, hindered peroxynitrite-mediated cell damage by preserving mitochondrial and endothelial function and consequently preventing apoptosis. The protective effect of (PhSe)2 was related to its ability to improve the intracellular redox state by increasing the expression of different isoforms of peroxiredoxins (Prx-1-3), efficient enzymes in peroxynitrite detoxification.
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina , Florianópolis, SC , Brazil.
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D000818:Animals; D001011:Aorta / Q000166:cytology; D001555:Benzene Derivatives / Q000494:pharmacology*; D002417:Cattle; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology; D004734:Energy Metabolism / Q000187:drug effects*; D006706:Homeostasis / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000737:chemistry; D016566:Organoselenium Compounds / Q000494:pharmacology*; D010084:Oxidation-Reduction; D054464:Peroxiredoxins / Q000378:metabolism*; D030421:Peroxynitrous Acid / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity
D001555:Benzene Derivatives; D016566:Organoselenium Compounds; D030421:Peroxynitrous Acid; C061132:diphenyldiselenide; C002385:linsidomine; D008981:Molsidomine; D054464:Peroxiredoxins
SIN-1; apoptosis; diphenyl diselenide; endothelial cells; mitochondria; mitochondrial dysfunction; nitric oxide homeostasis; nitroxidative stress; peroxiredoxin; peroxynitrite