酰基辅酶A：胆固醇酰基转移酶抑制剂对高密度脂蛋白诱导大鼠巨噬细胞泡沫细胞胆固醇流出的不同影响。

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

作者信息

Hakamata H, Miyazaki A, Sakai M, Sakamoto Y I, Matsuda H, Kihara K, Horiuchi S

机构信息

Department of Biochemistry, Kumamoto University School of Medicine, Japan.

出版信息

FEBS Lett. 1995 Apr 17;363(1-2):29-32. doi: 10.1016/0014-5793(95)00273-c.

DOI:10.1016/0014-5793(95)00273-c

PMID:7729547

Abstract

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.

摘要

当用乙酰化低密度脂蛋白（乙酰-LDL）将大鼠巨噬细胞转化为泡沫细胞，然后使其与高密度脂蛋白（HDL）及酰基辅酶A：胆固醇酰基转移酶抑制剂（58-035）反应时（顺序孵育系统），58-035并未增强HDL诱导的胆固醇流出。相反，当巨噬细胞在HDL和58-035同时存在的情况下暴露于乙酰-LDL时（同时孵育系统），58-035使HDL诱导的胆固醇流出增强了1.6倍。单独使用HDL时，同时孵育中的胆固醇流出比顺序孵育时大2倍。这些结果表明在同时孵育中存在一条有效的胆固醇流出途径，而在顺序孵育中不存在。我们将这条途径称为不依赖中性胆固醇酯水解酶的途径，其特征是溶酶体来源的胆固醇流出且无需重新酯化。