Effect of selenolipoic acid on peroxynitrite-dependent inactivation of NADPH-cytochrome P450 reductase.
Seleno-organic compounds are known as efficient "scavengers" of peroxynitrite (PN). Here we studied the protective effect of selenolipoic acid (SeLA), the seleno-containing analogue of lipoic acid, on peroxynitrite-dependent inactivation of NADPH-cytochrome P450 reductase. 3-Morpholinosydnonimine hydrochloride (SIN-1) was used as a source of peroxynitrite. The reductase was irreversibly inactivated by PN generated from SIN-1. The inactivation occurred with the rate constant of about 3 x 10(4) M-1 s-1. The presence of SeLA at low concentration (0.5 microM) led to synergistic increase of the reductase inactivation by PN. Our results suggest the formation of a reactive derivative of SeLA in the reaction of SeLA with PN, probably selenolseleninate, that mediates the aggravation of reductase inactivation. In the presence of SeLA, the inactivation was reversible under the action of thiols, allowing us to conclude that the observed action of SeLA may be considered as protective.
Sergeeva
S V
SV
Institute of Chemical Kinetics & Combustion, Novosibirsk, 630090, Russia. sergeeva@ns.kinetics.nsc.ru
Slepneva
I A
IA
Khramtsov
V V
VV
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008862:Microsomes, Liver / Q000201:enzymology; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009249:NADP / Q000494:pharmacology; D009251:NADPH-Ferrihemoprotein Reductase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D020030:Nitric Oxide Donors / Q000494:pharmacology; D030421:Peroxynitrous Acid / Q000378:metabolism*; D051381:Rats; D013438:Sulfhydryl Compounds / Q000737:chemistry; D008063:Thioctic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D020030:Nitric Oxide Donors; D013438:Sulfhydryl Compounds; D030421:Peroxynitrous Acid; D009249:NADP; C002385:linsidomine; D008063:Thioctic Acid; D008981:Molsidomine; D009251:NADPH-Ferrihemoprotein Reductase