Differential effects of an acyl‐coenzyme A: cholesterol acyltransferase inhibitor on HDL‐induced cholesterol efflux from rat macrophage foam cells

FEBS Letters

Kihara, Kohji¹  Sakamoto, Yu-Ichiro¹  Matsuda, Hirofumi¹  Sakai, Masakazu¹  Hakamata, Hideki¹  Horiuchi, Seikoh¹  Miyazaki, Akira¹ 

[1]Department of Biochemistry, Kumamoto University School of Medicine, Honjo 2-2-1, Kumamoto 860, Japan

关键词: Macrophage foam cell;    Cholesteryl ester cycle;    ACAT inhibitor;    High density lipoprotein;    Cholesterol efflux;    Intracellular cholesterol transport;    ACAT;    acyl-coenzyme A;    cholesterol acyltransferase;    HDL;    high density lipoprotein;    LDL;    low density lipoprotein;    acety-LDL;    acetylated LDL;    CE;    cholesteryl esters;    MFC;    macrophage foam cells;    BSA;    bovine serum albumin;    NCEH;    neutral cholesterol ester hydrolase;   

DOI  :  10.1016/0014-5793(95)00273-C

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

When rat macrophages were converted to foam cells with acetylated low density lipoprotein (acetyl-LDL) and then reacted with high density lipoprotein (HDL) and an inhibitor of acyl-coenzyme A:cholesterol acyltransferase (58-035) (sequential incubation system), 58-035 did not enhance HDL-induced cholesterol efflux. In contrast, when macrophages were exposed to acetyl-LDL in the presence of both HDL and 58-035 (simultaneous incubation system), HDL-induced cholesterol efflux was enhanced 1.6-fold by 58-035. Cholesterol efflux with HDL alone was 2-fold greater in simultaneous incubation than in sequential incubation. These results suggest the presence of an efficient cholesterol efflux pathway in simultaneous incubation which is not available in sequential incubation. This pathway, which we refer to as the neutral cholesterol ester hydrolase-independent pathway, is characterized by the efflux of lysosome-derived cholesterol without re-esterification.

【 授权许可】

Unknown