Effects of chronic alcohol treatment on the synthesis, sialylation, and disposition of nascent apolipoprotein E by peritoneal macrophages of rats

• Published in: The American journal of clinical nutrition 2000-07, Vol.72 (1), p.190-198
• Main Authors: GHOSH, P, HALE, E. A, MAYUR, K, SEDDON, J, LAKSHMAN, M. R
• Format: Article
• Language: English
• Subjects: Alcohol; Alcoholism and acute alcohol poisoning; Animals; Apolipoproteins E - biosynthesis; Apolipoproteins E - blood; Apolipoproteins E - chemistry; Biological and medical sciences; Cell Fractionation; Cells, Cultured; Cholesterol; Diet; Ethanol - administration & dosage; Ethanol - pharmacology; Glycosylation; Golgi Apparatus - metabolism; Macrophages, Peritoneal - drug effects; Macrophages, Peritoneal - metabolism; Macrophages, Peritoneal - secretion; Macrophages, Peritoneal - ultrastructure; Male; Medical sciences; Microsomes - metabolism; N-Acetylneuraminic Acid - analysis; N-Acetylneuraminic Acid - metabolism; Proteins; Rats; Rats, Wistar; Rodents; Toxicology
• ISSN: 0002-9165; 1938-3207
• DOI: 10.1093/ajcn/72.1.190

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. 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. 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. 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. 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.