Effect of selenolipoic acid on peroxynitrite-dependent inactivation of NADPH-cytochrome P450 reductase

Seleno-organic compounds are known as efficient "scavengers" of peroxynitri te (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 hy drochloride (SIN-1) was used as a source of peroxynitrite. The reductase wa s irreversibly inactivated by PN generated from SIN-1. The inactivation occ urred with the rate constant of about 3 x 10(4) M-1 s(-1). The presence of SeLA at low concentration (0.5 muM) led to synergistic increase of the redu ctase inactivation by PN. Our results suggest the formation of a reactive d erivative of SeLA in the reaction of SeLA with PN, probably selenolselenina te, that mediates the aggravation of reductase inactivation. In the presenc e of SeLA, the inactivation was reversible under the action of thiols, allo wing us to conclude that the observed action of SeLA may be considered as p rotective.