Effects of tributyltin on barrier functions in human intestinal Caco-2 cells.
Effects of tributyltin on barrier functions in human intestinal Caco-2 cells.
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DOI：
10.1016/j.bbrc.2004.01.147
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发表时间：
2004-03
影响因子：
3.1
通讯作者：
Masashi Tsukazaki;H. Satsu;Akira Mori;Y. Sugita‐Konishi;M. Shimizu
中科院分区：
文献类型：
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作者：
Masashi Tsukazaki;H. Satsu;Akira Mori;Y. Sugita‐Konishi;M. Shimizu
利用人肠Caco-2单层细胞研究三丁基锡（TBT）对人肠上皮细胞功能的影响。我们特别关注 TBT 对两种屏障功能的影响：作为物理屏障的紧密连接和作为生物屏障的 MDR1/P-糖蛋白。 TBT 处理明显丧失了单层完整性，并且 TBT 增加了细胞旁通透性。另一方面，通过测量罗丹明-123和道诺霉素的积累来检查P-糖蛋白的活性，通过延长TBT处理以浓度依赖性方式（1-100nM）增加。此外，Western 和 Northern 印迹证实这种增加伴随着 MDR1 mRNA 和蛋白质表达的增加。 TBT激活多药耐药转运蛋白P-糖蛋白，会通过改变药物药代动力学引起人体肠道紊乱。
The effect of tributyltin (TBT) on human intestinal epithelial cell functions was investigated by using human intestinal Caco-2 cell monolayers. We paid particular attention to the effect of TBT on two barrier functions: the tight junction as a physical barrier and MDR1/P-glycoprotein as a biological barrier. A loss of monolayer integrity was apparent from the TBT treatment and the paracellular permeability was increased by TBT. On the other hand, the activity of P-glycoprotein, which was examined by measuring the accumulation of Rhodamine-123 and daunomycin, was increased by prolonged TBT treatment in a concentration-dependent manner (1–100nM). Furthermore, it was clarified by Western and Northern blots that this increase was accompanied by the increased expression of MDR1 mRNA and protein. The activation of a multidrug resistance transporter P-glycoprotein by TBT would cause a disorder of the human intestines by changing the drug pharmacokinetics.