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Growth-rate-related and hydroxysterol-induced changes in membrane fluidity of cultured hepatoma cells: correlation with 3-hydroxy-3-methyl glutaryl CoA reductase activity.

Abstract
3-hydroxy-3-methylglutaryl-coenzyme A reductase (EC 1.1.1.3.4.) activity and cell membrane fluidity measured by fluorescence polarization using 1,6 diphenyl, 1,3,5-hexatriene as fluorescent probe have been concomitantly examined in HTC hepatoma cells, both in relation to growth rate and in response to treatment with hydroxylated sterols. A high level of HMG-CoA reductase activity was observed in cells at log phase of growth which progressively decreased to reach a sustained low level at stationary phase. Similarly, membrane fluidity markedly decreased in relation to growth rate. Hydroxylated sterols such as 7 beta-hydroxycholesterol or 25-hydroxycholesterol strongly inhibited HMG-CoA reductase activity whereas a water-soluble derivative of 7 beta-hydroxycholesterol sodium 3,7-bishemisuccinate had no effect. Within the same range of concentrations 7 beta-hydroxycholesterol and 25-hydroxycholesterol strongly decreased membrane fluidity when the water-soluble derivative was ineffective. Thus, the present results provide evidence for a correlation between the two tested parameters and suggest a dependency of HMG-CoA reductase activity on cell membrane fluidity.
AuthorsL Richert, M Castagna, J P Beck, S Rong, B Luu, G Ourisson
JournalBiochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 120 Issue 1 Pg. 192-8 (Apr 16 1984) ISSN: 0006-291X [Print] United States
PMID6538790 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • 7-hydroxycholesterol-3,7-bis(hemisuccinate)
  • Hydroxycholesterols
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Sterols
  • cholest-5-en-3 beta,7 alpha-diol
  • 25-hydroxycholesterol
  • Hydroxymethylglutaryl CoA Reductases
Topics
  • Animals
  • Cell Division
  • Cell Line
  • Hydroxycholesterols (pharmacology)
  • Hydroxymethylglutaryl CoA Reductases (metabolism)
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Liver Neoplasms, Experimental (enzymology, metabolism)
  • Membrane Fluidity (drug effects)
  • Sterols (pharmacology)

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