Effect of peroxisomal proliferators on microsomal prostaglandin A omega-hydroxylase.
Earlier, we reported the isolation of a cytochrome P-450 highly active in prostaglandin A (PGA) omega-hydroxylation (PGA omega-hydroxylase) from rabbit kidney cortex, small intestine, and colon microsomes. In the present studies, the effects of peroxisomal proliferating agents on the PGA omega-hydroxylase have been examined. Administration of clofibrate or di(2-ethylhexyl)phthalate (DEHP) resulted in a significant increase in the PGA1 omega-hydroxylase activity of kidney cortex, liver, and small intestine microsomes. Similar findings were also obtained for laurate hydroxylase activity in kidney and liver microsomes. Kidney PGA omega-hydroxylase (designated cytochrome P-450ka) was isolated and highly purified from clofibrate- or DEHP-treated rabbits, with a yield 3 times higher than that from untreated, or phenobarbital- or 3-methylcholanthrene-treated rabbits. Cytochrome P-450ka from clofibrate- or DEHP-treated rabbits exhibited the same properties as those from untreated rabbits. Guinea pig antiserum against cytochrome P-450ka strongly inhibited the omega-hydroxylation of PGA1 by kidney cortex microsomes from clofibrate-treated rabbits. The PGA1 omega-hydroxylase activity of clofibrate-treated liver microsomes was also inhibited by this antiserum, suggesting that a PGA omega-hydroxylase immunochemically related to cytochrome P-450ka exists in liver microsomes.
D000818:Animals; D002994:Clofibrate / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004051:Diethylhexyl Phthalate / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D007120:Immunochemistry; D007421:Intestine, Small / Q000201:enzymology; D007672:Kidney Cortex / Q000201:enzymology; D008830:Microbodies / Q000187:drug effects; D008861:Microsomes / Q000201:enzymology*; D008862:Microsomes, Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D010795:Phthalic Acids / Q000494:pharmacology*; D011817:Rabbits
D010795:Phthalic Acids; D003577:Cytochrome P-450 Enzyme System; D004051:Diethylhexyl Phthalate; D006899:Mixed Function Oxygenases; C026961:prostaglandin omega hydroxylases; D002994:Clofibrate