Inhibition of cholesteryl ester transfer protein by apolipoproteins, lipopolysaccharides, and cholesteryl sulfate.
Cholesteryl ester transfer protein (CETP) mediates the exchange of cholesteryl esters and triglycerides between lipoproteins in the plasma. In studies dealing with the mechanism of CETP-mediated lipid transfer, we have examined the effects of several classes of biomolecules, including apolipoproteins and related synthetic peptides, cholesteryl sulfate, and lipopolysaccharides. In all cases, the molecules were inhibitory and their effects were associated with modifications of either HDL, LDL, or both. However, the probable mechanisms were distinct for each class of inhibitor. Inhibition of lipid transfer activity by apolipoprotein A-I was correlated with an increase in the apolipoprotein A-I content of HDL but not LDL, whereas the primary effect of cholesteryl sulfate was associated with modification of LDL, and only modest alteration of HDL. Lipopolysaccharides were found to modify the size and charge properties of both LDL and HDL over the same concentration ranges that affected CETP activity, but might also interact directly with CETP. It is suggested from the present studies that a variety of biomolecules that can interact with lipoproteins under natural or pathological situations have the potential to modify CETP activity, which in turn could affect normal lipoprotein composition and distribution.
Connolly
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DT
Cardiovascular Diseases Research Department, Searle, St. Louis, MO 63167, USA.
Krul
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ES
Heuvelman
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D
Glenn
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KC
D000906:Antibodies / Q000494:pharmacology; D016632:Apolipoprotein A-I / Q000494:pharmacology; D001053:Apolipoproteins / Q000276:immunology / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism*; D002784:Cholesterol / Q000031:analogs & derivatives / Q000494:pharmacology; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006023:Glycoproteins; D006801:Humans; D050356:Lipid Metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D010455:Peptides / Q000494:pharmacology; D014280:Triglycerides / Q000378:metabolism
D000906:Antibodies; D016632:Apolipoprotein A-I; D001053:Apolipoproteins; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D006023:Glycoproteins; D008070:Lipopolysaccharides; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D010455:Peptides; D014280:Triglycerides; C035843:cholesterol glucuronide; D002784:Cholesterol; C007045:cholesteryl sulfate