[Effect of bezafibrate on lipoprotein secretion by cultured human hepatocytes]

The rate of synthesis and secretion of lipid and apoprotein components of lipoprotein fractions and of proteins of the nonlipoprotein fraction d greater than 1.21 g/ml by human hepatocytes in culture was determined. The cells were incubated for 18 hours in the media containing [14C] acetate or [3H]-marked leucine in the presence of bezafibrate or without it. VLDL, HDL and d greater than 1.21 g/ml fractions were separated by differential ultracentrifugation. The lipids were divided using thin-layer chromatography, and the apoprotein-using SDS-electrophoresis in polyacrylamide gel. Bezafibrate in the therapeutic concentration of 10 microM specifically inhibits apoprotein and VLDL lipid secretion. Lowered secretion of all VLDL apoproteins was revealed, which points to a decrease in the number of secreted particles. The effect of bezafibrate was found to be associated with the inhibition of the intracellular synthesis of lipids. The secretion of HDL proteins and of d greater than 1.21 g/ml fraction proteins was unchanged with 10 microM of bezafibrate.