EFFECTS OF 2 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 per oxisome proliferators than clofibrate, on the activities of dihydroxya cetone-phosphate acyl-transferase (DHAP-AT) and glycerol-3-phosphate a cyl-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 electrophor esis. 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-A T in these two fractions were increased by 6 to 11 times, as a result of hepatomegaly and peroxisome proliferation. In contrast, they were o nly slightly enhanced (x 1.1 to 2.2-fold) when determined at pH 7.4, T he magnitude of the effects of a fibrate treatment was, therefore, dep endent on the pH of the incubation medium. 2) Experiments of reversibi lity of enzyme induction reinforced the finding that the peroxisomal D HAP-AT activity is not specifically induced by ciprofibrate and fenofi brate. 3) Our results suggest the existence of a peroxisomal G3P-AT, n on-inducible by fibrates, in the rat liver. 4) Induction of peroxisoma l membrane-associated polypeptides with apparent molecular masses of 2 6-and 36-kDa was evidenced in stained electrophoretic gels of protein.