Oxysterol-activated LXRα/RXR induces hSR-BI-promoter activity in hepatoma cells and preadipocytes
Oxysterol-activated LXRα/RXR induces hSR-BI-promoter activity in hepatoma cells and preadipocytes
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DOI：
10.1016/s0006-291x(02)02760-2
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发表时间：
2002-12-20
影响因子：
3.1
通讯作者：
Berg, T
中科院分区：
文献类型：
--
作者：
Malerod, L;Juvet, LK;Berg, T
SR-BI介导HDL和细胞之间的胆固醇交换，并且是过量细胞胆固醇从肝外组织转运到肝脏（“胆固醇反向转运”）的关键因素，因此也是胆固醇稳态的关键因素。肝SR-BI介导HDL-胆固醇转移至肝细胞，在肝细胞中胆固醇可代谢为胆汁酸。LXR和SREBP是调节胆固醇代谢的关键因素。本研究的目的是确定这些转录因子是否参与SR-BI的调节。在这里，我们表明LXR α/RXR和LXR β/RXR诱导SR-BI在人类和小鼠肝癌细胞系中的转录，并在3 T3-L1前脂肪细胞中独立于SREBP-1。LXR/RXR反应定位在启动子区的-1200至-937范围内。凝胶迁移率变动分析证实，推定的LXR反应元件结合LXR α/RXR和LXR β/RXR异二聚体。(C)2002 Elsevier Science（美国）。All rights reserved.
SR-BI mediates exchange of cholesterol between HDL and cells, and is a crucial factor in the transport of excessive cellular cholesterol from extrahepatic tissues to the liver ("reverse cholesterol transport") and, therefore, also for cholesterol homeostasis. Hepatic SR-BI mediates transfer of HDL-cholesterol to the hepatocytes where cholesterol may be metabolised to bile acids. LXR and SREBP are key factors in the regulation of cholesterol metabolism. The purpose of the present study was to determine whether these transcription factors are involved in the regulation of SR-BI. Here we show that LXRalpha/RXR and LXRbeta/RXR induce SR-BI transcription in human and murine hepatoma cell lines, and in 3T3-L1 preadipocytes independently of SREBP-1. The LXR/RXR response was mapped within -1200 to -937 of the promoter region. Gel mobility shift analysis confirmed that the putative LXR response element bound LXRalpha/RXR and LXRbeta/RXR heterodimers. (C) 2002 Elsevier Science (USA). All rights reserved.