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  • Title: The effect of reagents that increase membrane fluidity on the activity of 3-hydroxyl-3-methyl glutaryl coenzyme A reductase in the CHO-K1 cell.
    Author: Sinensky M, Kleiner J.
    Journal: J Cell Physiol; 1981 Sep; 108(3):309-16. PubMed ID: 7197282.
    Abstract:
    The compounds cetyl trimethyl ammonium bromide (CTAB) and ethanol both decrease the order parameter of a spin probe embedded in cholesterol-lecithin liposomes, but CTAB produces lowering of the order parameter comparable to that produced by ethanol at a 10,000-fold lower concentration. Treatment of CHO-K1 cells with CTAB or ethanol at concentrations that produce comparable increases of membrane fluidity produce to 2- to 3-fold increase of microsomal membrane cholesterol to phospholipid ratio and a 2- to 3-fold increase of the activity of the rate-limiting enzyme of cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Cells treated with CTAB or ethanol show a progressively decreasing capacity to accumulate alpha-aminoisobutyric acid with increasing drug treatment, but cells pre-treated with CTAB are relatively resistant to the effects of CTAB on alpha-aminoisobutyrate transport. The increase in HMG-CoA reductase by CTAB or ethanol is not observed when these compounds are added directly to cell extracts but, rather, is only observed after 8 hours or exposure of intact cells to these drugs. Actinomycin D and cycloheximide treatment prevent the increase in enzyme activity, and the increase is also blocked in a regulatory mutant of the CHO-K1 cell with permanently repressed HMG-CoA reductase activity. These data are consistent with a homeoviscous adaptation mechanism in the CHO-K1 cell, in which increased activity of HMG-CoA reductase, through a process requiring RNA and protein synthesis, compensates for conditions that increase membrane fluidity by increased cellular cholesterol biosynthesis and cholesterol to phospholipid ratio.
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