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

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 M(r) 77,000, 61,000, 43,000 and 31,000, and a similar decrease in the concentrations of three mRNA species coding for proteins of M(r) 25,000, 24,000 and 19,000. Specific immunoprecipitation studies identified the proteins of M(r) 19,000, 43,000 and 77,000 as α(2μ)-globulin, 3-ketoacyl-CoA thiolase (EC 2.3.1.16) and enoyl-CoA hydratase (EC 4.2.1.17) respectively. Comparisons of the M(r) values suggest that the 61,000- and 31,000-M(r) proteins may be equivalent to two additional peroxisomal enzymes, namely catalase (M(r) 61,000) and uricase (M(r) 31,000). The identity of the mRNA species coding for the 25,000- and 24,000-M(r) proteins is at present unknown.