Cytochrome P-450 monooxygenase system. Localization in smooth muscle of rabbit aorta.
Cytochrome P-450 monooxygenase isozymes and NADPH-cytochrome P-450 reductase were detected in the microsomal fraction of rabbit aorta by immunoblotting and by enzymatic activity. The monomeric molecular weights of aortal proteins that cross-reacted with antibodies to cytochrome P-450 forms 2 or 6 and reductase were identical to those of the proteins purified from the liver. The induction of form 6 immunoreactive protein and O-deethylation of 7-ethoxyresorufin (a reaction catalyzed by form 6) was observed in aorta following treatment of rabbits with 2,3,7,8-tetrachlorodibenzo-p-dioxin or beta-naphthoflavone. The amount of reductase protein (equivalent to 22.4 +/- 3.2 activity units/mg of protein) correlated with the cytochrome c reductase activity (18.3 +/- 1.8 units/mg) and was the same for both treated and untreated rabbits. Consistent with immunoblot data, the amount of form 2 was insufficient for detection of activity (N-demethylation of benzphetamine). Significantly, removal of the endothelium, which was confirmed by light microscopy and by scanning electron microscopy, reduced by only 8 to 32% the specific enzymatic activity or content of immunoreactive proteins; only traces of protein or activity were recovered in the endothelial fraction. In studies of the vasculature, the potential of this metabolic pathway for the activation or detoxication of mutagens, carcinogens, toxins, or drugs and metabolism of endogenous substrates warrants consideration, especially in regard to the mutational events reported to be involved in the formation of atherosclerotic plaques.
D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D008297:Male; D008861:Microsomes / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D008970:Molecular Weight; D009131:Muscle, Smooth, Vascular / Q000201:enzymology*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D011817:Rabbits; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D000072317:Polychlorinated Dibenzodioxins; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D009251:NADPH-Ferrihemoprotein Reductase