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 beta-galactoside alpha 2,6- and alpha 2,3-sialyltransferases, respectively; (ii) a 67-69% reduction in the level of hepatic beta-galactoside alpha 2,6-sialyltransferase protein; and (iii) 41-46 and 6-28% reductions in the levels of the hepatic beta-galactoside alpha 2,6- and alpha 2,3-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 alpha 2,3- and alpha 2,6-linkage, respectively. When assessed by labeling semithin frozen sections of liver tissue with a fluorescent lectin specific for alpha 2,6-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.
Fayos
B E
BE
Department of Cell, Molecular and Structural Biology, Northwestern University Medical School, Chicago, Illinois 60611.
Bartles
J R
JR
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002995:Clofibric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004051:Diethylhexyl Phthalate / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D058607:Fibric Acids; D006023:Glycoproteins / Q000378:metabolism*; D000960:Hypolipidemic Agents / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000302:isolation & purification; D008830:Microbodies / Q000187:drug effects; D008970:Molecular Weight; D011743:Pyrimidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012795:Sialoglycoproteins / Q000096:biosynthesis* / Q000302:isolation & purification; D012799:Sialyltransferases / Q000096:biosynthesis*; D001616:beta-Galactosidase / Q000096:biosynthesis; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
D000924:Anticholesteremic Agents; D058607:Fibric Acids; D006023:Glycoproteins; D000960:Hypolipidemic Agents; D008562:Membrane Glycoproteins; D011743:Pyrimidines; D012333:RNA, Messenger; D012795:Sialoglycoproteins; D002995:Clofibric Acid; C006253:pirinixic acid; D004051:Diethylhexyl Phthalate; D012799:Sialyltransferases; D001616:beta-Galactosidase; C019304:ciprofibrate; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase