PMID: 18712089Aug 21, 2008Paper

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

Biomedit︠s︡inskai︠a︡ khimii︠a︡
A R MekhtievA Iu Misharin

Abstract

Novel synthetic oxysterols (22S,23S)-3beta-hydroxy-22,23-oxido-5alpha-ergost-8(14)-en-15-one (I) and (22R,23R)-3beta-hydroxy-22,23-oxido-5alpha-ergost-8(14)-en-15-one (II) influenced cholesteryl esters biosynthesis in human hepatoma Hep G2 cell line from [14C]acetate (85% and 180% compared to control at the concentrations of 5 microM). The level of cholesteryl esters biosynthesis in Hep G2 cells from [14C]oleate increased in the presence of ketosterol (I) in a dose dependent manner, whereas the level of cholesteryl esters biosynthesis in the presence of ketosterol (II) reached the maximal value (269+/-20% from control) at the concentration of 1 microM. In a cell free system ketosterol (I) increased the rate of ACAT-dependent cholesterol acylation like 25-hydroxycholesterol, however, ketosterol (II), efficiently stimulating initial rate of ACAT-catalyzed cholesterol esterification, caused in rapid inactivation of this enzyme.

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