24S-hydroxycholesterol induces cholesterol release from choroid plexus epithelial cells in an apical- and apoE isoform-dependent manner concomitantly with the induction of ABCA1 and ABCG1 expression
24S-hydroxycholesterol induces cholesterol release from choroid plexus epithelial cells in an apical- and apoE isoform-dependent manner concomitantly with the induction of ABCA1 and ABCG1 expression
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DOI：
10.1111/j.1471-4159.2006.04240.x
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发表时间：
2007-02-01
影响因子：
4.7
通讯作者：
Terasaki, Tetsuya
中科院分区：
文献类型：
--
作者：
Fujiyoshi, Masachika;Ohtsuki, Sumio;Terasaki, Tetsuya
脉络丛上皮细胞（CPE）释放胆固醇对CSF中的胆固醇稳态起着重要作用。本研究的目的是利用条件永生化的CPE细胞系（TR-CSFB 3）阐明CPE中参与胆固醇释放的分子以及肝脏X受体（LXR）对胆固醇释放的调控机制。检测大鼠脉络丛中LXR α、LXR β及其靶基因ATP结合盒转运体（ABC）A1、ABCG 1、ABCG 4和ABCG 5的mRNA表达。ABCA 1和ABCG 1蛋白表达于TR-CSFB 3细胞的质膜上。在用内源性LXR配体24 S-羟基胆固醇处理后，在TR-CSFB 3细胞中诱导ABCA 1和ABCG 1的表达。此外，载脂蛋白（apo）AI和高密度脂蛋白（HDL）介导的胆固醇释放到TR-CSFB 3细胞的顶侧，促进了这种治疗，而对基底侧不受影响。24 S-羟基胆固醇处理后，TR-CSFB 3细胞的apoE 3依赖性胆固醇释放比apoE 4依赖性胆固醇释放增强。这些结果表明，LXR激活通过ABCA 1和ABCG 1的功能诱导促进胆固醇从CPE释放到CSF中。apoE 3和apoE 4之间的差异表明CPE释放的胆固醇与神经退行性疾病的发展有关。
The release of cholesterol from choroid plexus epithelial cells (CPE) plays an important role in cholesterol homeostasis in the CSF. The purpose of this study was to clarify the molecules involved in cholesterol release in CPE and the regulation mechanisms of the cholesterol release by the liver X receptor (LXR) using a conditionally immortalized CPE line (TR-CSFB3). The mRNA expression of LXR alpha, LXR beta and their target genes, ATP-binding cassette transporter (ABC)A1, ABCG1, ABCG4 and ABCG5, were detected in rat choroid plexus. ABCA1 and ABCG1 protein were detected in the plasma membrane of TR-CSFB3 cells. Following treatment with 24S-hydroxycholesterol, an endogenous LXR ligand, the expression of ABCA1 and ABCG1 were induced in TR-CSFB3 cells. Moreover, apolipoprotein (apo)AI- and high-density lipoprotein (HDL)-mediated cholesterol release to the apical side of TR-CSFB3 cells was facilitated by this treatment, whereas that to the basal side was not affected. Following 24S-hydroxycholesterol treatment, apoE3-dependent cholesterol release from TR-CSFB3 cells was enhanced more than the apoE4-dependent release. These results suggest that LXR activation facilitates cholesterol release into the CSF from CPE through the functional induction of ABCA1 and ABCG1. The difference between apoE3 and apoE4 suggests that the cholesterol release from CPE is related to the development of neurodegenerative diseases.