REGULATION OF HEPATOCYTIC GLYCOPROTEIN SIALYLATION AND SIALYLTRANSFERASES BY PEROXISOME PROLIFERATORS

Short-term dietary exposure of rats to a representative member of each of the three classes of peroxisome proliferators was found to elicit: (i) 71-80 and 66-75% reductions in the specific activities of the hep atic beta-galactoside alpha2,6- and alpha2,3-sialyltransferases, respe ctively; (ii) a 67-69% reduction in the level of hepatic beta-galactos ide alpha2,6-sialyltransferase protein; and (iii) 41-46 and 6-28% redu ctions in the levels of the hepatic beta-galactoside alpha2,6- and alp ha2,3-sialyltransferase mRNAs, respectively. These changes were found to correlate with a reduction in the sialylation of the N-linked glyca ns of a prototypical hepatocytic sialoglycoconjugate, the integral pla sma membrane glycoprotein CE9, as was evident through: (i) a decrease in apparent molecular mass, (ii) a conversion to a more basic distribu tion of isoelectric points, and (iii) 56-72 and 33-44% decreases in th e ability to bind lectins specific for sialic acid in alpha2,3- and al pha2,6-linkage, respectively. When assessed by labeling semithin froze n sections of liver tissue with a fluorescent lectin specific for alph a2,6-linked sialic acid, the reduced sialylation observed for CE9 was found to extend to other hepatocytic glycoconjugates in the livers of peroxisome proliferator-treated rats.