Long-term ethanol exposure impairs glycosylation of both N- and O-glycosylated proteins in rat liver

摘要: Carbohydrate residues of glycoproteins play important roles in their functions. We have previously shown that long-term ethanol treatment rats alters the normal glycosylation pattern plasma transferrin and apolipoprotein (apo) E. Glycosylation proteins is a posttranslational process regulated by both glycosyltransferases glycosidases, resident enzymes hepatic subcellular organelles. In this investigation using rat apo E as model N- O-glycosylated proteins, respectively, we explored effects on (1) incorporation various labeled sugar precursors into these specific glycoproteins, (2) activities mannosyltransferase, galactosyltransferase, sialyltransferases, (3) synthetic rate N-acetyl glucosamine (GlcNAc) α2,6-sialyltransferase (2,6-ST). The relative ratio to leucine (glycosylation index) showed 43% (P < .01) decrease for mannosylation molecule at microsomal Golgi level group (AN) versus control (CN). For E, was reduced 48.9% 46.9% .01), AN CN. More importantly, sialation 86% .001) compared with Relative 35% A comparison key glycosylating liver mannosyltransferase galactosyltransferase were decreased 24.4% 21.1% whereas activity 2,6-ST markedly 52.9% This inhibitory effect 2,6-ST, since GlcNAc α-2,3-sialyltransferase [4,5-3H]-N-acetylgalactosamine (GalNAc) α-2,3-ST only 31.6% 4% (NS), same treatment. It further inhibition due concomitant 48% its caused Thus, our results clearly established leads marked step inhibiting 2,6-ST.