Reversible alteration of hepatic messenger RNA species for peroxisomal and non-peroxisomal proteins induced by the hypolipidaemic drug Wy-14,643

Abstract

Extensive peroxisomal proliferation in the hepatic parenchymal cells was observed when male rats were given a diet containing 0.1% Wy-14,643 [(4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid), a potent lipid-decreasing drug. This drug also caused a marked increase in the concentrations of the mRNA species coding for four proteins with Mr 77000, 61000, 43000 and 31000, and a similar decrease in the concentrations of three mRNA species coding for proteins of Mr 25000, 24000 and 19000. Specific immunoprecipitation studies identified the proteins of Mr 19000, 43000 and 77000 as alpha 2u-globulin, 3-ketoacyl-CoA thiolase (EC 2.3.1.16) and enoyl-CoA hydratase (EC 4.2.1.17) respectively. Comparisons of the Mr values suggest that the 61000- and 31000-Mr proteins may be equivalent to two additional peroxisomal enzymes, namely catalase (Mr 61000) and uricase (Mr 31000). The identity of the mRNA species coding for the 25000- and 24000-Mr proteins is at present unknown.