The effect of caveolin-1 on the synthesis and efflux of cholesterol in hepatoma cells and hepatocytes

Abstract

The effect of caveolin-1 on synthesis and efflux of cholesterol was studied using three cell systems. The McA-RH7777 cells were stably transfected with caveolin-1 previously. HepG2 cells were infected with a caveolin-1 adenovirus, and primary hepatocytes were isolated from homozygous and heterozygous caveolin-1 deficient and control mice. Overexpression of caveolin-1 resulted in an increase of cholesterol synthesis, and the absence of caveolin-1 resulted in a decrease in cholesterol synthesis. Cholesterol ester and phospholipid synthesis are not affected. The influence of caveolin-1 on efflux to HDL was small in the three cell models. Efflux of cholesterol to apoA-I was not significantly affected by caveolin-1 over expression. Caveolin-1 deficient hepatocytes had reduced cholesterol synthesis. Cholesterol efflux to HDL and exogenously added apoA-I decreased in the absence of apoA-I. Phospholipid and cholesterol lipidation of endogenously synthesized apoA-I was reduced in the absence of caveolin-1. Overall, caveolin-1 deficiency had more consistent effect on cholesterol metabolism than over expression of caveolin-1, suggesting that the basal level of caveolin-1 in hepatocytes is probably sufficient to regulate cholesterol homeostasis and cellular transport.