Cholesterol sulfate uptake and outflux in cultured human keratinocytes

Summary

Cholesterol sulfate-cholesterol homeostasis in the epidermis may be important for normal desquamation. Recent evidence from cell-culture studies indicates that cholesterol sulfate inhibits sterologenesis by inhibiting the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme in cholesterol synthesis. For cholesterol sulfate in the stratum corneum to function as a feedback regulator of epidermal sterologenesis, it must have the capacity enter cells. In these studies, uptake and outflux of cholesterol sulfate was examined in cultured human foreskin keratinocytes, and compared with uptake and outflux of cholesterol and 25-hydroxycholesterol, as well as with sterol uptake by another cell type, the skin fibroblast. The uptake of the free (not lipoprotein-associated) form of all three sterols was not consistent with a receptor-mediated process. Although the cholesterol sulfate uptake was approximately three-fold less than that of 25-hydroxycholesterol, it was nearly seven-fold greater than that of cholesterol itself. Whereas 25-hydroxycholesterol was rapidly washed out of keratinocytes in outflux experiments, both cholesterol and cholesterol sulfate tended to remain cell-associated. These studies demonstrate that cholesterol sulfate is readily taken up by keratinocytes, in which it may be in a position to modulate cellular lipid metabolism.