Growth-related modulation of human skin fibroblast cholesterol distribution and metabolism

The relationship between cell growth state and the metabolism and distribution of cellular cholesterol was studied in human skin fibroblasts. Cells made quiescent by serum starvation maintained a smaller fraction of total free cholesterol in a pool susceptible to oxidation by added cholesterol oxidase compared to growing cells. The growth-related differences in the distribution of free cholesterol were magnified in cells which were preincubated in low-density lipoprotein. These latter cells hydrolyzed cholesteryl ester which had accumulated in the presence of LDL, resulting in an increased level of cellular free cholesterol after growth activation. By preincubating cells in [3H]cholesterol linoleate-labeled LDL, it could be demonstrated that activation of cell growth facilitated the appearance of LDL-derived cholesterol in a pool accessible to cholesterol oxidase. These studies suggest that onset of growth in fibroblasts leads to a redistribution of free cholesterol from intracellular to plasma membrane compartments. Furthermore, activation of cell growth in cholesterol loaded cells leads to the net conversion of cholesteryl ester to free cholesterol and most of the latter is in the plasma membrane.