ARYL SULFOTRANSFERASE ACTIVITY IN CHOLESTATIC RAT-LIVER INDUCED BY COMMON BILE-DUCT LIGATION

We have studied the effect of cholestasis on the activities of hepatic aryl sulfotransferase (AST) isozymes I-II and III-IV in rats. ASTs I-II and III-IV activities were determined in cytosol, mitochondria and microsomal preparations isolated from the cholestatic rat liver, and in the rat serum after common bile duct ligation for a period of 42 days. The values of K-m and V-max of these hepatic isozymes were also measured by using 3'-phosphoadenosine 5'-phosphosulfate as the substrate. The activities of both cytosolic ASTs I-II and III-IV in the cholestatic rat liver showed significant decrease after the 14th day through the 42nd day of the bile duct ligation (ranging from 29%-50% decrease) compared to the activities from the sham operated control. However, quite contrary to it, the activities of the mitochondrial ASTs I-II and III-IV in the cholestatic liver started to increase at the 7th day and the high activities persisted until the 42nd day after the ligation with peak activities at the 14th day (increase of 82% for the former and 66% for the latter isozymes, respectively). However, in the case of microsomal enzyme, only the AST III-IV activity increased between the 2nd and 42nd days after the ligation, while the AST I-II activity did not change significantly during these time period. Enzyme kinetic analyses of AST isozymes indicated that V-max for the mitochondrial ASTs III and III-IV, and the microsomal AST III-IV increased significantly, although the K,values for these isozymes were about the same as control. When analysed serum ASTs I-II and III-IV, the activities were also increased with peak activities at 2-3 days after the ligation. These results, therefore, suggest that the biosynthesis of liver particulates-bound ASTs are induced in respons to cholestasis, and that the elevations of serum isozyme activities are most likely due to a reflection of the increased cholestatic liver enzymes.