Prevention of peroxisomal proliferation by carnitine palmitoyltransferase inhibitors in cultured rat hepatocytes and in vivo.
1. The induction of peroxisomal beta-oxidation activities by bezafibrate in cultured rat hepatocytes and in the rat in vivo was prevented by inhibitors of carnitine acyltransferase, e.g. 2-bromopalmitate, 2-[5-(4-chlorophenyl)pentyl]oxirane-2-carboxylate or 2-tetradecylglycidic acid. 2. The prevention of peroxisomal proliferation by carnitine palmitoyltransferase inhibitors could not be accounted for by inhibition of mitochondrial beta-oxidation, since 2-bromo-octanoate, acting as an inhibitor of beta-oxidation, did not prevent the induction of peroxisomal activities in cultured rat hepatocytes. 3. The putative role of the acylcarnitine derivative of bezafibrate was analysed by studying the formation of bezafibroylcarnitine with bezafibroyl-CoA as substrate. However, no bezafibroylcarnitine formation was demonstrated in the presence of rat liver preparations capable of catalysing transfer to carnitine of medium- or long-chain fatty acids. 4. The prevention of peroxisomal proliferation by carnitine acyltransferase inhibitors may help in dissecting the causal relationship between the multiple effects mediated by peroxisomal proliferators.
Hertz
R
R
Department of Biochemistry, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Bar-Tana
J
J
D000217:Acyltransferases / Q000037:antagonists & inhibitors*; D000818:Animals; D001629:Bezafibrate / Q000494:pharmacology*; D002210:Caprylates / Q000494:pharmacology; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors*; D002478:Cells, Cultured; D004852:Epoxy Compounds / Q000494:pharmacology; D005227:Fatty Acids / Q000494:pharmacology; D005990:Glycerol / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D008830:Microbodies / Q000187:drug effects / Q000201:enzymology; D010168:Palmitates / Q000494:pharmacology*; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats
D002210:Caprylates; D004852:Epoxy Compounds; D005227:Fatty Acids; D010168:Palmitates; D010169:Palmitic Acids; C022776:2-bromopalmitate; C019279:2-bromooctanoic acid; D019308:Palmitic Acid; C033891:ethyl 2-(5-(4-chlorophenyl)pentyl)oxiran-2-carboxylate; D000217:Acyltransferases; D002334:Carnitine O-Palmitoyltransferase; D005990:Glycerol; C021756:2-tetradecylglycidic acid; D001629:Bezafibrate