title: Bisphenol A promotes cholesterol absorption in Caco-2 cells by up-regulation of NPC1L1 expression.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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. fengdan3@mail.sysu.edu.cn.
authors.forename: Dan
authors.initials: D
authors.lastname: Feng
authors.affiliation: Department of Cardiology, Affiliated NanHai Hospital of Southern Medical University, Foshan, 528200, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zou
authors.affiliation: 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.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Xuechun
authors.initials: X
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Peiyang
authors.initials: P
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Minqi
authors.initials: M
authors.lastname: Lu
mesh_terms: D001559:Benzhydryl Compounds / Q000633:toxicity*; D001692:Biological Transport / Q000187:drug effects; D018938:Caco-2 Cells; D002784:Cholesterol / Q000378:metabolism*; D004785:Environmental Pollutants / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006937:Hypercholesterolemia / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D007408:Intestinal Absorption; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D026901:Membrane Transport Proteins; D010636:Phenols / Q000633:toxicity*; D015533:Transcriptional Activation; D015854:Up-Regulation; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D002784:Cholesterol; D004785:Environmental Pollutants; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D010636:Phenols; C410800:NPC1L1 protein, human; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Bisphenol A; Caco-2 cells; Cholesterol absorption; Hypercholesterolemia; Niemann-Pick C1-like 1; Sterol regulatory element binding protein-2