Direct protective effect of NAD(P)H:quinone reductase against menadione-induced chemiluminescence of postmitochondrial fractions of mouse liver.
In the presence of NADPH and oxygen, menadione (2-methyl-1,4-naphthoquinone) elicits low level red chemiluminescence from rodent liver preparations. This chemiluminescence is believed to arise from the formation of active oxygen species that are generated when the quinone undergoes oxidative cycling. The obligatory two-electron reduction of quinones to hydroquinones catalyzed by NAD(P)H:(quinone-acceptor) oxidoreductase (EC 1.6.99.2) has been implicated in the suppression of this photoemission by competing with oxidative cycling (Wefers, H., Komai, T., Talalay, P., and Sies, H. (1984) FEBS Lett. 169, 63-66 and references therein). Thus, in previous studies, we showed that treatment of mice with BHA (2(3)-tert-butyl-4-hydroxyanisole), which elevates cytosolic quinone reductase activity about 10-fold, reduced menadione-dependent chemiluminescence of hepatic post-mitochondrial supernatant fractions, whereas inhibition of quinone reductase by dicoumarol greatly intensified light emission. We demonstrate here that addition of pure quinone reductase to this preparation suppresses menadione-dependent chemiluminescence, and that the protective effect of 2(3)-tert-butyl-4-hydroxyanisole treatment can be accounted for completely by the induction of this specific enzyme. These results provide conclusive evidence that in this system the protective action of anticarcinogenic antioxidants is entirely attributable to the elevation of the level of an electrophile-processing enzyme.
D000818:Animals; D002083:Butylated Hydroxyanisole / Q000494:pharmacology; D001728:Dicumarol / Q000494:pharmacology; D005260:Female; D008099:Liver / Q000648:ultrastructure*; D008163:Luminescent Measurements; D008297:Male; D051379:Mice; D016660:NAD(P)H Dehydrogenase (Quinone); D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D011808:Quinone Reductases / Q000378:metabolism*; D011809:Quinones / Q000378:metabolism; D013367:Submitochondrial Particles / Q000187:drug effects*; D014812:Vitamin K / Q000494:pharmacology*
D011809:Quinones; D014812:Vitamin K; D002083:Butylated Hydroxyanisole; D009249:NADP; D001728:Dicumarol; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases; D010100:Oxygen