Effects of chronic alcohol treatment on the synthesis, sialylation, and disposition of nascent apolipoprotein E by peritoneal macrophages of rats.
BACKGROUND
Plasma apolipoprotein (apo) E, a sialoprotein, plays an important role in reverse cholesterol transport. Previously, we showed that chronic alcohol consumption impairs glycosylation of apo E in rat liver. Peritoneal macrophages are another significant apo E synthesis site.


OBJECTIVE
The main purpose of this study was to determine the effects of chronic alcohol feeding of rats on the synthesis, sialylation, and sialic acid content of macrophage apo E and its ability to bind to the HDL(3) molecule in vitro.


METHODS
Rats were fed an alcoholic diet or an isoenergetic control diet for 8 wk, after which peritoneal macrophages isolated from them were cultured and analyzed for apo E metabolism.


RESULTS
Macrophages from alcohol-fed rats accumulated 33.3% more (P < 0.05) cholesterol than did those from control rats when incubated with acetylated LDL. These macrophages showed a 51-57% lower relative sialylation rate of apo E (P < 0.001) but no significant difference in relative protein synthetic rate. The sialic acid content of the intracellular and secreted forms of apo E was reduced by 41.8% (P < 0.001) and 50.3% (P < 0.001), respectively, with chronic alcohol treatment. Secretion of newly synthesized apo E was impaired by 53.7% (P < 0.001) and 26. 1% (P < 0.001) in the absence and presence of HDL in the medium, respectively. Macrophages of alcohol-treated rats secreted apo E with 47.6-67.2% lower (P < 0.001) HDL(3) binding ability; binding ability was restored completely by resialylation of the desialylated apo E.


CONCLUSIONS
In rats, an alcohol-mediated decrease in sialylation rate resulting in loss of sialic acid residues in apo E impairs the ability of apo E to bind to HDL and consequently in defective reverse cholesterol transport.
Ghosh
P
P
Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, USA.
Hale
E A
EA
Mayur
K
K
Seddon
J
J
Lakshman
M R
MR
D000818:Animals; D001057:Apolipoproteins E / Q000096:biosynthesis* / Q000097:blood / Q000737:chemistry*; D002458:Cell Fractionation; D002478:Cells, Cultured; D004032:Diet; D000431:Ethanol / Q000008:administration & dosage* / Q000494:pharmacology; D006031:Glycosylation; D006056:Golgi Apparatus / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008861:Microsomes / Q000378:metabolism; D019158:N-Acetylneuraminic Acid / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D001057:Apolipoproteins E; D000431:Ethanol; D019158:N-Acetylneuraminic Acid