Sterol efflux mediated by endogenous macrophage ApoE expression is independent of ABCA1
Sterol efflux mediated by endogenous macrophage ApoE expression is independent of ABCA1
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DOI：
10.1161/hq1201.100242
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发表时间：
2001-12-01
影响因子：
8.7
通讯作者：
Mazzone, T
中科院分区：
文献类型：
--
作者：
Huang, ZH;Lin, CY;Mazzone, T
甾醇外排对维持细胞胆固醇稳态有重要作用，可能涉及多种途径介导这种外排。最近，一个重要的作用已被归因于ABCA 1在促进脂质流出细胞，包括巨噬细胞。到细胞外无脂载脂蛋白。巨噬细胞在细胞中相对独特，因为它们表达载脂蛋白E（apoE）作为主要蛋白质产物，并且apoE的这种内源性表达增加巨噬细胞的固醇和磷脂流出。本研究旨在检测巨噬细胞内源性apoE表达介导的甾醇外排是否依赖于ABCA 1的表达。通过比较apoE表达的J774细胞（J774 E（+））与不表达apoE的亲本细胞（J774 E（-）），促进了这些研究。与J774 E（-）细胞相比，J774 E（+）细胞的甾醇外排更高，但这些细胞类型之间的外排增量并没有通过用CAMP诱导ABCA 1表达而增加。然而，CAMP诱导ABCA 1确实增加了来自两种细胞类型的固醇流出到外源性添加的apoA 1。ABCA 1活性抑制剂显著降低（40%-50%）经cAMP和apoA 1处理的J774 E（+）和J774 E（-）细胞的甾醇流出。这种抑制剂没有。然而，由于内源性apoE的表达，减少了甾醇流出的增加。这些研究的结果表明，在巨噬细胞内源性表达apoE介导的甾醇流出的增量不依赖于ABCA 1的表达或活性。
Sterol efflux importantly contributes to preservation of cellular cholesterol homeostasis, and multiple pathways may be involved for mediating such efflux. Recently, an important role has been ascribed to ABCA1 in facilitating lipid efflux from cells, including macrophages. to extracellular lipid-free apolipoproteins. Macrophages are relatively unique among cells because they express apoprotein E (apoE) as a major protein product, and this endogenous expression of apoE increases sterol and phospholipid efflux from macrophages. The studies in this article were designed to test whether the sterol efflux mediated by the endogenous expression of apoE in macrophages was dependent on ABCA1 expression. These studies were facilitated by comparing apoE-expressing J774 cells (J774E(+)) with nonexpressing parental cells (J774E(-)). Sterol efflux was higher from J774E(+) cells compared with J774E(-) cells, but the increment in efflux between these cell types was not increased by induction of ABCA1 expression with CAMP. Induction of ABCA1 with CAMP, however, did increase sterol efflux to exogenously added apoA1 from both cell types. Inhibitors of ABCA1 activity significantly reduced (by 40% to 50%) sterol efflux from both J774E(+) and J774E(-) cells treated with CAMP and apoA1. This inhibitor did not. however, reduce the increment in sterol efflux due to the expression of endogenous apoE. The results of these studies indicate that the increment in sterol efflux mediated by the endogenous expression of apoE in macrophages does not depend on ABCA1 expression or activity.