Interaction of swine lipoproteins with the low density lipoprotein receptor in human fibroblasts.
HDLc, a cholesterol-rich lipoprotein that accumulates in the plasma of cholesterol-fed swine, was shown to resemble functionally human and swine low density lipoprotein in its ability to bind to the low density lipoprotein receptor in monolayers of cultured human fibroblasts. This binding occurred even though HDLc lacked detectable apoprotein B, which is the major protein of low density lipoprotein. After it was bound to the low density lipoprotein receptor, HDLc, like human and swine low density lipoprotein, delivered its cholesterol to the cells, and this, in turn, caused a suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, an activation of the cholesterol-esterifying system, and a net accumulation of free and esterified cholesterol within the cells. Swine HDLc, like human high density lipoprotein, did not bind to the low density lipoprotein receptor nor did it elicit any of the subsequent metabolic events. HDLc, like human low density lipoprotein, was incapable of producing a metabolic effect in fibroblasts derived from a subject with the homozygous form of familial hypercholesterolemia, which lack low density lipoprotein receptors. These results indicate that two lipoproteins that have been associated with athersclerosis--low density lipoprotein in humans and HDLc in cholesterol-fed swine--both can cause the accumulation of cholesterol and cholesteryl esters within cells through an interaction with the low density lipoprotein receptor.
D000818:Animals; D001665:Binding Sites; D002788:Cholesterol Esters / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D006937:Hypercholesterolemia / Q000378:metabolism; D007700:Kinetics; D008074:Lipoproteins / Q000097:blood; D008077:Lipoproteins, LDL / Q000378:metabolism*; D009829:Oleic Acids / Q000378:metabolism; D011485:Protein Binding; D011955:Receptors, Drug; D013552:Swine
D002788:Cholesterol Esters; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D009829:Oleic Acids; D011955:Receptors, Drug