Growth-rate-related and hydroxysterol-induced changes in membrane fluidity of cultured hepatoma cells: correlation with 3-hydroxy-3-methyl glutaryl CoA reductase activity.
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.
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D006888:Hydroxycholesterols / Q000494:pharmacology; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008114:Liver Neoplasms, Experimental / Q000201:enzymology / Q000378:metabolism*; D008560:Membrane Fluidity / Q000187:drug effects*; D013261:Sterols / Q000494:pharmacology*
C041101:7-hydroxycholesterol-3,7-bis(hemisuccinate); D006888:Hydroxycholesterols; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D013261:Sterols; C011724:cholest-5-en-3 beta,7 alpha-diol; C007997:25-hydroxycholesterol; D006903:Hydroxymethylglutaryl CoA Reductases