[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].

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.

• Authors: A R Mekhtiev, N I Kozlova, V V Skripnik, A Iu Misharin
• Journal: Biomeditsinskaia khimiia (Biomed Khim) 2008 May-Jun Vol. 54 Issue 3 Pg. 341-8 ISSN: 2310-6972 [Print] Russia (Federation)
• PMID: 18712089 (Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 3beta-hydroxy-22,23-oxido-5alpha-ergost-8(14)-en-15-one
• Cholesterol Esters
• Sterols
• Sterol O-Acyltransferase

Topics

• Carcinoma, Hepatocellular
• Cell Line, Tumor
• Cell-Free System
• Cholesterol Esters (biosynthesis)
• Humans
• Stereoisomerism
• Sterol O-Acyltransferase (metabolism)
• Sterols
• Structure-Activity Relationship