Feng Dan, Zou Jun, Zhang Shanshan, Li Xuechun, Li Peiyang, Lu Minqi
Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Preventive Medicine, School of Public Health, Sun Yat-sen University (Northern Campus), 74 Zhongshan Road 2, Guangzhou, Guangdong Province, 510080, China.
Department of Cardiology, Affiliated NanHai Hospital of Southern Medical University, Foshan, 528200, China.
Lipids Health Dis. 2017 Jan 6;16(1):2. doi: 10.1186/s12944-016-0395-0.
Bisphenol 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.
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.
We 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.
This 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.
双酚A（BPA）是一种人类普遍接触的环境化学物质，已被证明具有高胆固醇血症作用，但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主要作用，本研究旨在探讨BPA是否影响肠道Caco-2细胞中的胆固醇吸收。
将Caco-2细胞用不同浓度的BPA预处理24小时，然后与放射性胶束胆固醇孵育2小时。通过液体闪烁法定量放射性胆固醇的吸收。通过蛋白质印迹法和定量聚合酶链反应分析尼曼-匹克C1样1（NPC1L1）和固醇调节元件结合蛋白2（SREBP-2）的表达。
我们发现汇合的Caco-2细胞表达NPC1L1，并且细胞中的胆固醇吸收受到NPC1L1特异性抑制剂依泽替米贝的抑制。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NPC1L1蛋白和NPC1L1 mRNA水平的显著增加有关。此外，BPA对胆固醇吸收和NPC1L1表达的刺激作用可通过阻断SREBP-2途径来预防。
本研究提供了首个证据，表明BPA促进肠道细胞中的胆固醇吸收，且BPA的刺激作用至少部分由SREBP-2-NPC1L1信号通路介导。
