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 a 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 α‐aminoisobutyric acid with increasing drug treatment, but cells pre‐treated with CTAB are relatively resistant to the effects of CTAB on α‐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 of 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.