Search resultsCholesterol efflux to high-density lipoproteins and apolipoprotein A-I phosphatidylcholine complexes is inhibited by ethanol: Role of apolipoprotein structure and cooperative interaction of phosphatidylcholine and cholesterol
Title
Cholesterol efflux to high-density lipoproteins and apolipoprotein A-I phosphatidylcholine complexes is inhibited by ethanol: Role of apolipoprotein structure and cooperative interaction of phosphatidylcholine and cholesterol
Publication type
Journal Article
Year of Publication
2000
Authors
Journal
Biochemistry
Volume
39
Issue
34
Pagination
10599 - 10606
Date published
2000
ISBN
00062960 (ISSN)
Keywords
alcohol, alcohol consumption, Alcohol Drinking, Alcoholism, animal cell, Animalia, Animals, Apolipoprotein A-I, apolipoprotein A1, article, Biological Transport, Active, Cardiovascular Diseases, Cholesterol, cholesterol transport, Clone Cells, conformational transition, Ergosterol, Ethanol, fibroblast, fluorescence polarization, high density lipoprotein, Humans, Lipoproteins, HDL, nonhuman, phosphatidylcholine, Phosphatidylcholines, priority journal, protein conformation, protein lipid interaction, rat, Rats, Tryptophan
Abstract
There is a substantial body of evidence showing that moderate alcohol consumption is associated with a reduced risk of cardiovascular morbidity and mortality. One of the factors thought to contribute to this reduction in risk is an increase in the level of high-density lipoproteins (HDL) correlated with alcohol consumption. However, HDL levels are elevated in heavy drinkers, but their risk of vascular disease is greater compared with that of moderate drinkers. Ethanol at concentrations observed in heavy drinkers and alcoholics may directly act on HDL and apolipoproteins and in turn modify cholesterol efflux. In this paper, we show that ethanol significantly inhibited cholesterol efflux from fibroblasts to HDL and to apolipoprotein A-I (apoA-I) complexed with phosphatidylcholine (PC). Ethanol significantly inhibited binding of PC to apoA-I, inhibited incorporation of cholesterol only when apoA-I contained PC, and did not alter incorporation of cholesterol into HDL. ApoA-I structure was altered by ethanol as monitored by steady-state fluorescence polarization of tryptophan residues. The absence of ethanol effects on incorporation of cholesterol into HDL versus inhibition of cholesterol incorporation into the apoA-I-PC complex suggests that the effects of ethanol on cholesterol efflux mediated by HDL involve interaction with the cell surface and that efflux mediated by the apoA-I-PC complex is a combination of aqueous diffusion and contact with the cell surface. In addition, effects of ethanol on apoA-I suggest that pre-β-HDL or lipid-free apoA-I may be more perturbed by ethanol than mature HDL, and such effects may be pathophysiological with respect to the process of reverse cholesterol transport in heavy drinkers and alcoholics.