title: Suppression of synthesis and esterification of cholesterol and stimulation of low density lipoprotein receptor activity by polyoxyethylated cholesterol in cultured human fibroblasts.
abstract: In cultured skin fibroblasts from normal and homozygous familial hypercholesterolemic subjects, a water-soluble polyoxyethylated derivative of cholesterol suppresses the incorporation of [2-14C]acetate into cholesterol and decreases the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme of cholesterol synthesis. The effect of this compound on low density lipoprotein (LDL) receptor-mediated activities (binding, internalization, and degradation of LDL) and on cholesterol ester formation was compared to that of LDL and 25-hydroxycholesterol. In normal fibroblasts preincubated in lipoprotein-deficient serum, LDL or 25-hydroxycholesterol decreased cholesterol synthesis and LDL receptor activity and increased cholesterol ester formation. In contrast, polyoxyethylated cholesterol stimulated LDL receptor activity, inhibited cholesterol ester formation mediated by LDL and 25-hydroxycholesterol, and inhibited the activity of acyl-CoA:cholesterol acyltransferase in cell extracts. Polyoxyethylated cholesterol had no effect on the low level of LDL receptor activity of homozygous hypercholesterolemic fibroblasts but stimulated the half-normal activity of heterozygous cells.
mesh_terms: D002478:Cells, Cultured; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000378:metabolism; D002788:Cholesterol Esters / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000494:pharmacology*; D012867:Skin / Q000378:metabolism*; D002785:Sterol O-Acyltransferase / Q000378:metabolism
chemical_list: D002788:Cholesterol Esters; D008077:Lipoproteins, LDL; C023044:polyoxyethylated cholesterol; D011092:Polyethylene Glycols; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D002785:Sterol O-Acyltransferase