Dominant expression of ATP-binding cassette transporter-1 on basolateral surface of Caco-2 cells stimulated by LXR/RXR ligands
Dominant expression of ATP-binding cassette transporter-1 on basolateral surface of Caco-2 cells stimulated by LXR/RXR ligands
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DOI：
10.1016/s0006-291x(02)00853-7
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发表时间：
2002-08-23
影响因子：
3.1
通讯作者：
Matsuzawa, Y
中科院分区：
文献类型：
--
作者：
Ohama, T;Hirano, K;Matsuzawa, Y
ATP结合盒转运蛋白-1（ABCA 1）是丹吉尔病的病因之一，丹吉尔病是一种家族性血浆高密度脂蛋白（HDL）缺乏症。已知该分子在多种组织和器官中表达，包括小肠、肝脏和血管中的巨噬细胞。最近的体内研究表明，ABCA 1在肠道胆固醇的流动中起着一定的作用。了解ABCA 1在肠道中的作用的主要问题之一是肠上皮细胞中的表达模式。为了解决这个问题，我们研究了ABCA 1在Caco-2细胞中的表达和调控，特别是关注ABCA 1可能的极化表达。ABCA 1的表达在分化过程中以及在添加9-cis-RA和22-R-羟基胆固醇（22-OH）的LXR/RXR的刺激下上调。当9-cis-RA和22-OH刺激时，载脂蛋白AI介导的胆固醇流出主要朝向极化细胞的基底外侧。细胞表面的生物素化实验，随后的Western印迹分析表明，ABCA 1的基底侧表面上的显着显性表达，这是明确证实了由共聚焦激光扫描显微镜。总之，本研究表明，ABCA 1主要表达在所测试的Caco-2细胞的基底外侧表面上，这表明该分子可能至少在LXR/RXR配体刺激时在胆固醇的基底外侧运动中发挥作用。(C)2002 Elsevier Science（美国）。All rights reserved.
ATP-binding cassette transporter-1 (ABCA1) is a cause of Tangier disease, which is a familial deficiency of plasma high density lipoproteins (HDL). This molecule is known to be expressed in the multiple tissues and organs including small intestines, liver, and macrophages in the blood vessels. Recent in vivo studies suggested that ABCA1 plays some roles in the flux of cholesterol in the intestines. One of the major questions to understand the roles of ABCA1 in the intestines is the expression pattern in the intestinal epithelial cells. To address this issue, we have investigated the expression and regulation of ABCA1 in Caco-2 cells cultured on Transwell as a model, especially focusing on possible polarized expression of ABCA1 The expression of ABCA1 was up-regulated during the differentiation and under the stimulation of LXR/RXR by the addition of 9-cis-retinoic acid (9-cis-RA) and 22-R-hydroxycholesterol (22-OH). Apolipoprotein-AI-mediated cholesterol efflux was dominant toward the basolateral side of polarized cells when stimulated by 9-cis-RA and 22-OH. The cell surface biotinylation experiment followed by Western blot analyses demonstrated a markedly dominant expression of ABCA1 on the basolateral surface, which was clearly confirmed by the confocal laser scanning microscopy. In conclusion, the present study demonstrates that ABCA1 is dominantly expressed on the basolateral surface of Caco-2 cells tested, suggesting that this molecule may play a role in the basolateral movement of cholesterol at least when stimulated by LXR/RXR ligands. (C) 2002 Elsevier Science (USA). All rights reserved.