Effects of compactin, mevalonate and low-density lipoprotein on 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity and low-density-lipoprotein-receptor activity in the human hepatoma cell line Hep G2
article
Compactin, an inhibitor of HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase, decreased cholesterol synthesis in intact Hep G2 cells. However, after the inhibitor was washed away, the HMG-CoA-reductase activity determined in the cell homogenate was found to be increased. Also the high-affinity association of LDL (low-density lipoprotein) to Hep G2 cells was elevated after incubation with compactin. Lipoprotein-depleted serum, present in the incubation medium, potentiated the compactin effect compared with incubation in the presence of human serum albumin. Addition of either mevalonate or LDL prevented the compactin-induced rise in activities of both HMG-CoA reductase and LDL receptor in a comparable manner. It is concluded that in this human hepatoma cell line, as in non-transformed cells, both endogenous mevalonate or mevalonate-derived products and exogenous cholesterol are able to modulate the HMG-CoA reductase activity as well as the LDL-receptor activity. Chemicals/CAS: cholesterol, 57-88-5; compactin, 73573-88-3; hydroxymethylglutaryl coenzyme A reductase, 37250-24-1; mevalonic acid, 150-97-0; Cholesterol, 57-88-5; compactin, 73573-88-3; Hydroxymethylglutaryl CoA Reductases, EC 1.1.1.-; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent, EC 1.1.1.34; Lipoproteins, LDL; Mevalonic Acid, 150-97-0; Naphthalenes; Receptors, Cell Surface; Receptors, LDL
Topics
albumincompactinlipoprotein receptorlow density lipoproteinmevalonic acidradioisotopedrug inhibitiondrug mechanismin vitro studyliverliver cell carcinomalow density lipoprotein i 125AnimalCell LineCholesterolHumanHydroxymethylglutaryl CoA ReductasesHydroxymethylglutaryl-CoA Reductase InhibitorsHydroxymethylglutaryl-CoA-Reductases, NADP-dependentLipoproteins, LDLLiver Neoplasms, ExperimentalMevalonic AcidNaphthalenesReceptors, Cell SurfaceReceptors, LDL
TNO Identifier
229533
ISSN
0264-6021
Source
Biochemical Journal, 222(1), pp. 35-39.
Pages
35-39
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