Instituto de Agroquímica y Tecnología de Alimentos (CSIC) , Av. Agustín Escardino, 7, 46980 Paterna, Valencia, Spain.
Chem Res Toxicol. 2012 Feb 20;25(2):446-53. doi: 10.1021/tx200491f. Epub 2012 Jan 26.
Inorganic arsenic (iAs) [As(III)+As(V)] is a drinking water contaminant, and human exposure to these arsenic species has been linked with a wide range of health effects. The main path of exposure is the oral route, and the intestinal epithelium is the first physiological barrier that iAs must cross in order to be absorbed. However, there is a lack of information about intestinal iAs absorption. The aim of this study was to evaluate the participation of certain transporters [glucose transporters (GLUT and SGLT), organic anion transporting polypeptides (OATPs), aquaporins (AQPs), and phosphate transporters (NaPi and PiT)] in intestinal absorption of As(V) and As(III), using the Caco-2 cell line as a model of the intestinal epithelium. For this purpose, the effects of chemical inhibition and gene silencing of the transporters of interest on iAs uptake were evaluated, and also the differential expression of these transporters after treatment with iAs. The results show that chemical inhibition using rifamycin SV (OATP inhibitor), phloridzin (SGLT inhibitor), phloretin (GLUT and AQP inhibitor), and copper sulfate (AQP inhibitor) leads to a significant reduction in the apparent permeability and cellular retention of As(III). RT-qPCR indicates up-regulation of GLUT2, GLUT5, OATPB, AQP3, and AQP10 after exposure to As(III), while exposure to As(V) increases the expression of sodium-dependent phosphate transporters, especially NaPiIIb. Gene silencing of OATPB, AQP10, and GLUT5 for As(III) and NaPiIIb for As(V) significantly reduces uptake of the inorganic forms. These results indicate that these transporters may be involved in intestinal absorption of iAs.
无机砷（iAs）[As(III)+As(V)]是饮用水污染物，人类接触这些砷物种与广泛的健康影响有关。主要暴露途径是口服途径，而肠道上皮是 iAs 必须穿过才能被吸收的第一个生理屏障。然而，关于肠道 iAs 吸收的信息却很少。本研究旨在评估某些转运体[葡萄糖转运体（GLUT 和 SGLT）、有机阴离子转运多肽（OATPs）、水通道蛋白（AQPs）和磷酸盐转运体（NaPi 和 PiT）]在 As(V)和 As(III)肠吸收中的参与，使用 Caco-2 细胞系作为肠道上皮模型。为此，评估了化学抑制和感兴趣的转运体基因沉默对 iAs 摄取的影响，以及用 iAs 处理后这些转运体的差异表达。结果表明，使用利福霉素 SV（OATP 抑制剂）、根皮苷（SGLT 抑制剂）、根皮素（GLUT 和 AQP 抑制剂）和硫酸铜（AQP 抑制剂）进行化学抑制会导致 As(III)的表观渗透率和细胞保留率显著降低。RT-qPCR 表明，暴露于 As(III)后 GLUT2、GLUT5、OATPB、AQP3 和 AQP10 的表达上调，而暴露于 As(V)增加了钠依赖性磷酸盐转运体的表达，尤其是 NaPiIIb。针对 As(III)的 OATPB、AQP10 和 GLUT5 以及针对 As(V)的 NaPiIIb 的基因沉默显著降低了无机形式的摄取。这些结果表明，这些转运体可能参与了 iAs 的肠道吸收。
