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.