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 hepatic β- galactoside α2,6- and α2,3-sialyltransferases, respectively; (ii) a 67-69% reduction in the level of hepatic β-galactoside α2,6-sialyltransferase protein; and (iii) 41-46 and 6-28% reductions in the levels of the hepatic β-galactoside α2,6- and α2,3-sialyltransferase mRNAs, respectively. These changes were found to correlate with a reduction in the sialylation of the N- linked glycans of a prototypical hepatocytic sialoglycoconjugate, the integral plasma membrane glycoprotein CE9, as was evident through: (i) a decrease in apparent molecular mass, (ii) a conversion to a more basic distribution of isoelectric points, and (iii) 56-72 and 33-44% decreases in the ability to bind lectins specific for sialic acid in α2,3- and α2,6- linkage, respectively. When assessed by labeling semi-thin frozen sections of liver tissue with a fluorescent lectin specific for α2,6-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.