Long-term ethanol exposure impairs glycosylation of both N- and O-glycosylated proteins in rat liver.
Carbohydrate residues of glycoproteins play important roles in their functions. We have previously shown that long-term ethanol treatment in rats alters the normal glycosylation pattern of plasma transferrin and apolipoprotein (apo) E. Glycosylation of proteins is a posttranslational process that is regulated by both glycosyltransferases and glycosidases, the resident enzymes of hepatic subcellular organelles. In this investigation using rat transferrin and apo E as model N- and O-glycosylated proteins, respectively, we have explored the effects of long-term ethanol treatment on the (1) incorporation of various labeled sugar precursors into these specific glycoproteins, (2) activities of mannosyltransferase, galactosyltransferase, and sialytransferases, and (3) hepatic synthetic rate of N-acetyl glucosamine (GlcNAc) alpha 2,6-sialyltransferase (2,6-ST). The relative ratio of labeled sugar to leucine incorporation (glycosylation index) showed a 43% (P < .01) decrease for relative mannosylation of transferrin molecule at both the microsomal and Golgi level in the ethanol group (AN) versus the control group (CN). For apo E, relative mannosylation was reduced by 48.9% (P < .01) and 46.9% (P < .01), respectively, at the microsomal and Golgi level in the AN versus CN. More importantly, relative sialation of transferrin was reduced by 86% (P < .001) in AN as compared with CN. Relative sialation of apo E was reduced by 35% (P < .01) in AN as compared with CN.(ABSTRACT TRUNCATED AT 250 WORDS)
Ghosh
P
P
Lipid Research Laboratory, Department of Veterans Affairs Medical Center, Washington, DC 20422, USA.
Liu
Q H
QH
Lakshman
M R
MR
D000818:Animals; D001835:Body Weight; D002451:Cell Compartmentation; D000431:Ethanol / Q000494:pharmacology*; D006023:Glycoproteins / Q000378:metabolism*; D006031:Glycosylation / Q000187:drug effects; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D006023:Glycoproteins; D000431:Ethanol