Effects of two peroxisome proliferators (ciprofibrate and fenofibrate) on peroxisomal membrane proteins and dihydroxyacetone-phosphate acyl-transferase activity in rat liver.
The effects of ciprofibrate and fenofibrate, which are more potent peroxisome proliferators than clofibrate, on the activities of dihydroxyacetone-phosphate acyl-transferase (DHAP-AT) and glycerol-3-phosphate acyl-transferase (G3P-AT) were studied at the two pH optima 5.5 and 7.4 in subcellular fractions of rat liver, and in solubilized peroxisomal membranes (PMP) as well. Protein was also analyzed by gel electrophoresis. 1) Under the conditions of the specific activity of peroxisomal acyl-CoA oxidase (CN(-)-ACO) being increased (8 to 9-fold), there was no specific induction of the DHAP-AT activity when measured at pH 5.5 in purified peroxisomes and PMP. However, the total activities of DHAP-AT in these two fractions were increased by 6 to 11 times, as a result of hepatomegaly and peroxisome proliferation. In contrast, they were only slightly enhanced (x 1.1 to 2.2-fold) when determined at pH 7.4. The magnitude of the effects of a fibrate treatment was, therefore, dependent on the pH of the incubation medium. 2) Experiments of reversibility of enzyme induction reinforced the finding that the peroxisomal DHAP-AT activity is not specifically induced by ciprofibrate and fenofibrate. 3) Our results suggest the existence of a peroxisomal G3P-AT, non-inducible by fibrates, in the rat liver. 4) Induction of peroxisomal membrane-associated polypeptides with apparent molecular masses of 26- and 36-kDa was evidenced in stained electrophoretic gels of protein.
Causeret
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C
Laboratoire de Biologie Moléculaire et Cellulaire, Faculté des Sciences Mirande, Université de Bourgogne, Dijon, France.
Bentejac
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M
Clemencet
M C
MC
Bugaut
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M
D000217:Acyltransferases / Q000096:biosynthesis; D000818:Animals; D002995:Clofibric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D011345:Fenofibrate / Q000494:pharmacology*; D058607:Fibric Acids; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D000960:Hypolipidemic Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008830:Microbodies / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D058607:Fibric Acids; D000960:Hypolipidemic Agents; D008565:Membrane Proteins; D002995:Clofibric Acid; D000217:Acyltransferases; D005992:Glycerol-3-Phosphate O-Acyltransferase; C020051:glycerone-phosphate O-acyltransferase; C019304:ciprofibrate; D011345:Fenofibrate