12(R)-hydroxyeicosatetraenoic acid synthesis by 3-methylcholanthrene- and clofibrate-inducible cytochrome P450 in porcine ciliary epithelium.
Porcine ciliary epithelial microsomes synthesized 12[S]-hydroxy-5, 8, 10, 14-eicosatetraenoic acid (12[S]-HETE) from arachidonic acid by a membrane-bound lipoxygenase and 12[R]-isomer by the cytochrome P450-dependent monooxygenase system. The activity to form 12(R)-isomer was markedly enhanced by 3-methylcholanthrene and clofibrate. Both basal and induced levels of 12(R)-HETE synthesizing activity were considerably higher in nonpigmented epithelial cells than in pigmented cells of the ciliary processes. The induced activity was suppressed by polyclonal antibodies raised against purified cytochrome P450 IA1 and NADPH-P450 reductase but not by substrates for clofibrate-inducible omega/omega-1 hydroxylases (P450 IVA-mediated). These results suggest that 12(R)-HETE synthesis by porcine ciliary microsomes may be mediated by a cytochrome P450 of the IA family.
Asakura
T
T
Department of Ophthalmology, Wayne State University School of Medicine Detroit, MI 48201.
Shichi
H
H
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000818:Animals; D002478:Cells, Cultured; D002924:Ciliary Body / Q000187:drug effects / Q000378:metabolism*; D002994:Clofibrate / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis*; D008748:Methylcholanthrene / Q000494:pharmacology*; D008861:Microsomes / Q000378:metabolism; D013237:Stereoisomerism; D013552:Swine
D006893:Hydroxyeicosatetraenoic Acids; D008748:Methylcholanthrene; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D003577:Cytochrome P-450 Enzyme System; D002994:Clofibrate