title: Suppression of 3-hydroxy-3-methylglutaryl-CoA reductase by low density lipoproteins produced in vitro by lipoprotein lipase action on nonsuppressive very low density lipoproteins.
abstract: Very low density lipoproteins (VLDL), Sf60 to 400, from normolipemic individuals do not suppress 3-hydroxy-3-methylglutaryl-CoA reductase activity in cultured normal human fibroblasts at concentrations 20-fold higher than those of low density lipoproteins (LDL) that give total suppression. To determine if these VLDL contain all of the structural elements necessary for receptor-mediated suppression, they were converted in vitro with bovine milk lipoprotein lipase to low density lipoproteins. These LDL-like lipoproteins were as effective in suppression as LDL isolated directly from plasma, with half-maximal and complete suppression at 1 and 4 microgram of cholesterol ml-1. Neither native LDL nor LDL produced in vitro suppressed receptor-negative fibroblasts. We conclude that action of lipoprotein lipase on VLDL leads to a rearrangement of lipoprotein components that permits interaction of LDL produced in vitro with the LDL-specific cell surface receptor of fibroblasts and subsequent suppression of 3-hydroxy-3-methylglutaryl-CoA reductase.
mesh_terms: D002478:Cells, Cultured; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006937:Hypercholesterolemia / Q000201:enzymology; D007700:Kinetics; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008079:Lipoproteins, VLDL; D008297:Male; D008970:Molecular Weight; D012867:Skin / Q000201:enzymology
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D008071:Lipoprotein Lipase