The Effects of (22S,23S)- and (22R,23R)-3-Hydroxy-22,23-Oxido-5a-Ergost-8(14)-en-15-ones on Biosynthesis of Cholesteryl Esters and Activity of Acyl-CoA: Cholesterol Acyl Transferase in Hep G2 Cells

摘要

Novel synthetic oxysterols (22S,23S)-3β-hydroxy-22,23-oxido-5a-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 cholesterylesters from [~(14)Clacetate (85% and 180% of control at 5 μMconcentration) in the human hepatoma Hep G2 cellline. Ketosterol (I) increased the level of cholesteryl ester biosynthesis from [~(14)C]oleate in Hep G2 cells adose dependent manner, whereas the level of cholesteryl esters biosynthesis in the presence of ketosterol (II)reached the maximal value (269 ± 20% of control) at 1μM concentration of this compound. In a cell free systemketosterol (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, fol-lowed by rapid inactivation of this enzyme.