Defective glycosylation of cholesteryl ester transfer protein in plasma from alcohol abusers.
OBJECTIVE
Alcohol consumption reduces the carbohydrate content of some glycoproteins, e.g. carbohydrate-deficient transferrin. The aim of this study was to investigate if there is such an alcohol-induced glycosylation defect in plasma cholesteryl ester transfer protein (CETP). A defect in the posttranslational glycosylation of CETP may affect its structure and electrical charge and may therefore affect its function. CETP activity is low in alcohol abusers.


METHODS
We studied the effect of alcohol consumption on CETP properties in 10 alcohol abusers and 10 control subjects. CETP was partially purified from lipoprotein-free plasma by FPLC using a Phenyl-Sepharose column. Isoelectric focusing, polyacrylamide gel electrophoresis, and western blotting were performed for partially purified CETP.


RESULTS
CETP had a lower molecular weight in the alcohol abusers than in the controls (range 50.6-84.0 kDa in the alcohol abusers vs 51.3-85.0 kDa in the controls). CETP purified from alcohol abusers had a higher isoelectric point, indicating a lower negative charge on the surface of the protein than in the controls' CETP. A similar effect was observed when control CETP was incubated with neuraminidase, an enzyme which is known to remove sialic acid from glycoproteins.


CONCLUSIONS
We conclude that CETP from alcohol abusers may have a glycosylation defect due to defective sialylation caused posttranslationally by alcohol itself or its metabolite acetaldehyde. The defective glycosylation of CETP associated with altered binding to lipoproteins may lead to the low CETP activity observed previously in alcoholic subjects.
Liinamaa
M Johanna
MJ
Department of Internal Medicine, University of Oulu, PO Box 5000, 90014 Oulu, Finland. johanna.liinamaa@oulu.fi
Hannuksela
Minna L
ML
Rämet
Maria E
ME
Savolainen
Markku J
MJ
D000437:Alcoholism / Q000097:blood* / Q000276:immunology / Q000503:physiopathology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D015153:Blotting, Western; D002352:Carrier Proteins / Q000097:blood*; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL / Q000097:blood; D006023:Glycoproteins / Q000097:blood*; D006031:Glycosylation; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male
D000911:Antibodies, Monoclonal; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D006023:Glycoproteins; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL