Effects of HDL subclasses on 3-hydroxy-3-methylglutaryl coenzyme A reductase in human fibroblasts.
Monolayer cultures of normal human fibroblasts were used to study the effects of the main subclasses of high-density lipoproteins, HDL2 and HDL3, on 3-hydroxy-3-methylglutaryl CoA reductase (EC 1.1.1.34) activity. In this system, HDL3 (d = 1.125-1.210 g/cm3) specifically induced HMG-CoA reductase activity. Evaluation of culture dynamics revealed that enzyme induction was restricted to the stationary phase of growth. When the cells were incubated with HDL2 (d = 1.063-1.125 g/cm3), suppression of reductase activity was observed. Mixtures of HDL2 and HDL3 suppressed reductase activity when HDL2 was greater than 35% of the total HDL. The suppressive effects of HDL2 were abolished by treatment with cyclohexanedione and restored by regeneration of the arginyl residues, suggesting an apoprotein-mediated suppressive mechanism. These observations show that the cellular effects of HDL depend upon the stage of cell growth and the ratio of HDL subclasses in HDL as usually isolated.
D002453:Cell Cycle; D002478:Cells, Cultured; D002784:Cholesterol / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000096:biosynthesis*; D025782:Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent; D008075:Lipoproteins, HDL / Q000502:physiology*; D053439:Lipoproteins, HDL2; D053440:Lipoproteins, HDL3
D008075:Lipoproteins, HDL; D053439:Lipoproteins, HDL2; D053440:Lipoproteins, HDL3; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D025782:Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent