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.
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.
D000621:Aminoisobutyric Acids / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D002593:Cetrimonium Compounds / Q000494:pharmacology*; D002784:Cholesterol / Q000096:biosynthesis; D006224:Cricetinae; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D008560:Membrane Fluidity / Q000187:drug effects*; D010053:Ovary; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*
D000621:Aminoisobutyric Acids; D002593:Cetrimonium Compounds; D000644:Quaternary Ammonium Compounds; D000431:Ethanol; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases