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Regulation of squalene synthetase in human hepatoma cell line Hep G2 by sterols, and not by mevalonate-derived non-sterols.

Abstract
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 microM 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.
AuthorsL H Cohen, E van Miert, M Griffioen
JournalBiochimica et biophysica acta (Biochim Biophys Acta) Vol. 1002 Issue 1 Pg. 69-73 (Mar 14 1989) ISSN: 0006-3002 [Print] Netherlands
PMID2538145 (Publication Type: Journal Article)
Chemical References
  • Androstenes
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipoproteins, HDL
  • Lipoproteins, LDL
  • Sterols
  • mevastatin
  • 3-beta-(2-(diethylamino)ethoxy)androst-5-en-17-one
  • Cholesterol
  • Lovastatin
  • Oxidoreductases
  • Farnesyl-Diphosphate Farnesyltransferase
  • Isomerases
  • Intramolecular Transferases
  • lanosterol synthase
  • Mevalonic Acid
Topics
  • Androstenes (pharmacology)
  • Carcinoma, Hepatocellular (enzymology)
  • Cholesterol (biosynthesis)
  • Farnesyl-Diphosphate Farnesyltransferase (metabolism)
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Intramolecular Transferases
  • Isomerases (antagonists & inhibitors)
  • Lipoproteins, HDL (pharmacology)
  • Lipoproteins, LDL (pharmacology)
  • Liver Neoplasms (enzymology)
  • Lovastatin (analogs & derivatives, pharmacology)
  • Mevalonic Acid (pharmacology)
  • Oxidoreductases (metabolism)
  • Sterols (metabolism)
  • Tumor Cells, Cultured

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