Bisphenol A promotes cholesterol absorption in Caco-2 cells by up-regulation of NPC1L1 expression.
Bisphenol A promotes cholesterol absorption in Caco-2 cells by up-regulation of NPC1L1 expression.
复制标题
双酚 A 通过上调 NPC1L1 表达促进 Caco-2 细胞中胆固醇的吸收
DOI：
10.1186/s12944-016-0395-0
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发表时间：
2017-01-06
影响因子：
4.5
通讯作者：
Lu M
中科院分区：
文献类型：
--
作者：
Feng D;Zou J;Zhang S;Li X;Li P;Lu M
研究背景双酚A（BPA）是一种常见的环境污染物，具有高胆固醇血症的作用，其分子机制尚不清楚。由于肠道胆固醇吸收在维持全身胆固醇稳态中起着重要作用，本研究旨在研究BPA是否影响肠道Caco-2细胞的胆固醇吸收。研究方法：用不同浓度的BPA预处理Caco-2细胞24 h，再与放射性胶束胆固醇孵育2 h。通过液体闪烁定量放射性胆固醇的吸收。Western blot和qPCR.ResultsWe发现，融合Caco-2细胞表达NPC 1 L1，NPC 1 L1特异性抑制剂依折麦布可抑制Caco-2细胞对胆固醇的吸收。然后，我们用0.1-10 nM BPA预处理细胞24小时，发现1和10 nM剂量的BPA促进胆固醇吸收。此外，我们发现BPA诱导的胆固醇吸收促进与NPC 1 L1蛋白和NPC 1 L1 mRNA水平的显著增加相关。此外，BPA对胆固醇吸收和NPC 1 L1表达的刺激作用可以通过阻断SREBP-2途径来阻止。结论该研究首次证明BPA促进肠细胞胆固醇吸收，并且BPA的刺激作用至少部分由SREBP-2-NPC 1 L1信号通路介导。
BackgroundBisphenol A (BPA), an commonly exposed environmental chemicals in humans, has been shown to have a hypercholesterolemic effect with molecular mechanism not clear. Since intestinal cholesterol absorption plays a major role in maintaining total body cholesterol homeostasis, the present study is to investigate whether BPA affects cholesterol absorption in the intestinal Caco-2 cells. Methods: The Caco-2 cells were pretreated with BPA at different concentrations for 24 h and then incubated with radioactive micellar cholesterol for 2 h. The absorption of radioactive cholesterol was quantified by liquid scintillation. The expression of Niemann-Pick C1-like 1 (NPC1L1) and sterol regulatory element binding protein-2 (SREBP-2) was analyzed by Western blot and qPCR.ResultsWe found that confluent Caco-2 cells expressed NPC1L1, and the absorption of cholesterol in the cells was inhibited by ezetimibe, a specific inhibitor of NPC1L1. We then pretreated the cells with 0.1–10 nM BPA for 24 h and found that BPA at 1 and 10 nM doses promoted cholesterol absorption. In addition, we found that the BPA-induced promotion of cholesterol absorption was associated with significant increase in the levels of NPC1L1 protein and NPC1L1 mRNA. Moreover, the stimulatory effects of BPA on cholesterol absorption and NPC1L1 expression could be prevented by blockade of the SREBP-2 pathway.ConclusionsThis study provides the first evidence that BPA promotes cholesterol absorption in the intestinal cells and the stimulatory effect of BPA is mediated, at least in part, by SREBP-2-NPC1L1 signaling pathway.