Cytochrome P-450 involvement in the NADPH-dependent lipid peroxidation in human placental mitochondria.
The NADPH-dependent lipid peroxidation in human placental mitochondria has been found to be inhibited strongly by amphenone B, aminoglutethimide and carbon monoxide, inhibitors of cytochrome P-450-mediated reactions, but was hardly affected by respiratory chain inhibitors. Cytochrome c, an exogenous electron acceptor which is known to compete with cytochrome P-450 for the reducing equivalents, showed an inhibitory effect on NADPH-dependent lipid peroxidation. The observed NADPH-dependent superoxide generation was also strongly inhibited by amphenone B and aminoglutethimide. Moreover, the lipid peroxidation in placental mitochondria was demonstrated to be stimulated by xanthine/xanthine oxidase added as superoxide generating system. This peroxidation was not affected by amphenone B and aminoglutethimide. On the other hand, the superoxide dismutase was found to inhibit both the xanthine oxidase- and NADPH-dependent lipid peroxidation. These data provide evidence that cytochrome P-450 is involved in NADPH-dependent mitochondrial lipid peroxidation. It is suggested that superoxide liberated from cytochrome P-450, in combination with iron, may be responsible for initiation of NADPH-dependent lipid peroxidation in human placental mitochondria.
Klimek
J
J
Department of Biochemistry, Academic Medical School, Gdansk, Poland.
D000616:Aminoglutethimide / Q000494:pharmacology; D002074:Butanones / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003574:Cytochrome c Group / Q000494:pharmacology; D006358:Hot Temperature; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009249:NADP / Q000378:metabolism*; D010920:Placenta / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000378:metabolism
D002074:Butanones; D003574:Cytochrome c Group; D000616:Aminoglutethimide; D008315:Malondialdehyde; D009249:NADP; D003577:Cytochrome P-450 Enzyme System; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase