Regulation of squalene synthetase in human hepatoma cell line Hep G2 by sterols, and not by mevalonate-derived non-sterols
article
Incubations of Hep G2 cells for 18 h with human low-density lipoprotein (LDL) resulted in a decrease of squalene synthetase activity, whereas heavy high-density lipoprotein (hHDL) stimulated the activity. Simultaneous addition of LDL abolished the hHDL-induced stimulation, indicating that manipulating the regulatory sterol pool within the cells influenced the enzyme activity. Blocking the endogenous cholesterol synthesis either at the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase site with compactin or at the 2,3-oxidosqualene cyclase site with the inhibitor U18666A gave rise to an elevation of the squalene synthetase activity. Simultaneous addition of mevalonate abolished the compactin-induced increase. However, at total blockade of sterol synthesis by 30 μM U18666A, added compactin and/or mevalonate did not change the enzyme activity further. It was concluded that sterols regulate the squalene synthetase activity, whereas, in contrast with the regulation of the HMG-CoA reductase activity in Hep G2 cells, mevalonate-derived non-sterols did not influence this enzyme.
Chemicals/CAS: 3beta (2 diethylaminoethoxy)androst 5 en 17 one, 3039-71-2; compactin, 73573-88-3; hydroxymethylglutaryl coenzyme A reductase (NADPH), 9028-35-7; mevalonic acid, 150-97-0; Androstenes; Cholesterol, 57-88-5; compactin, 73573-88-3; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Isomerases, EC 5.; lanosterol synthase, EC 5.4.99.7; Lipoproteins, HDL; Lipoproteins, LDL; Lovastatin, 75330-75-5; Mevalonic Acid, 150-97-0; Oxidoreductases, EC 1.; Squalene Synthetase, EC 1.3.-; Sterols; U 18666A, 3039-71-2
Chemicals/CAS: 3beta (2 diethylaminoethoxy)androst 5 en 17 one, 3039-71-2; compactin, 73573-88-3; hydroxymethylglutaryl coenzyme A reductase (NADPH), 9028-35-7; mevalonic acid, 150-97-0; Androstenes; Cholesterol, 57-88-5; compactin, 73573-88-3; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Isomerases, EC 5.; lanosterol synthase, EC 5.4.99.7; Lipoproteins, HDL; Lipoproteins, LDL; Lovastatin, 75330-75-5; Mevalonic Acid, 150-97-0; Oxidoreductases, EC 1.; Squalene Synthetase, EC 1.3.-; Sterols; U 18666A, 3039-71-2
Topics
3beta (2 diethylaminoethoxy)androst 5 en 17 onecompactinhigh density lipoproteinhydroxymethylglutaryl coenzyme a reductase (nadph)low density lipoproteinmevalonic acidsqualene synthetasecell cultureenzyme regulationhepatoma cellhumanhuman cellpriority journalAndrostenesCarcinoma, HepatocellularCholesterolHumanHydroxymethylglutaryl-CoA Reductase InhibitorsIsomerasesLipoproteins, HDLLipoproteins, LDLLiver NeoplasmsLovastatinMevalonic AcidOxidoreductasesSqualene SynthetaseSterolsTumor Cells, Cultured
TNO Identifier
230810
ISSN
00052760
Source
Biochimica et Biophysica Acta - Lipids and Lipid Metabolism, 1002(1), pp. 69-73.
Pages
69-73
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