The effects of (22S,23S)- and (22R,23R)-3[beta]-hydroxy-22,23-oxido-5[alpha]-ergost-8(14)-en-15-ones on biosynthesis of cholesteryl esters and activity of acyl-CoA:Cholesterol acyl transferase in Hep G2 cells

Novel synthetic oxysterols (22S,23S)-3β-hydroxy-22,23-oxido-5α-ergost-8(14)-en-15-one (I) and (22R,23R)-3β-hydroxy-22,23-oxido-5α-ergost-8(14)-en-15-one (II) influenced biosynthesis of cholesteryl esters from [14C]acetate (85% and 180% of control at 5 μM concentration) in the human hepatoma Hep G2 cell line. Ketosterol (I) increased the level of cholesteryl ester biosynthesis from [14C]oleate in Hep G2 cells in a dose dependent manner, whereas the level of cholesteryl esters biosynthesis in the presence of ketosterol (II) reached the maximal value (269±20% of control) at 1 μM concentration of this compound. In a cell free system ketosterol (I) increased the rate of ACAT-dependent cholesterol acylation similar to 25-hydroxycholesterol, however, ketosterol (II)), efficiently stimulated an initial rate of ACAT-catalyzed cholesterol esterification, followed by rapid inactivation of this enzyme. [PUBLICATION ABSTRACT]