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Differential effects of an acyl‐coenzyme A: cholesterol acyltransferase inhibitor on HDL‐induced cholesterol efflux from rat macrophage foam cells
Author(s) -
Hakamata Hideki,
Miyazaki Akira,
Sakai Masakazu,
Sakamoto Yu-Ichiro,
Matsuda Hirofumi,
Kihara Kohji,
Horiuchi Seikoh
Publication year - 1995
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)00273-c
Subject(s) - incubation , efflux , cholesterol , sterol o acyltransferase , reverse cholesterol transport , biochemistry , chemistry , coenzyme a , acyltransferase , lipoprotein , enzyme , reductase
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.