Effects of P-glycoprotein inhibitors on transepithelial transport of cadmium in cultured renal epithelial cells, LLC-PK1 and LLC-GA5-COL 150
Effects of P-glycoprotein inhibitors on transepithelial transport of cadmium in cultured renal epithelial cells, LLC-PK1 and LLC-GA5-COL 150
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DOI：
10.1016/j.tox.2004.11.015
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发表时间：
2005-03-01
期刊：
影响因子：
4.5
通讯作者：
Sakata, M
中科院分区：
文献类型：
--
作者：
Kimura, O;Endo, T;Sakata, M
本研究利用lc - pk1细胞和p -糖蛋白（P-gp）过表达的lc - pk1细胞（lc - ga5 - col 150细胞）分别研究内源性和过表达的P-gp对镉（Cd）的分泌转运。在通透膜上培养的细胞单层在37度下用1 muM CdCl2从顶端或基底外侧孵育60分钟。lc - ga5 - col150细胞中Cd的基底外侧向根尖转运量是根尖向基底外侧转运量的1.7倍，而lc - pk1细胞中Cd的根尖和基底外侧转运量基本相同。P-gp单克隆抗体UIC2显著降低了LLC-PK1和llc - ga5 - col150细胞中Cd从基底外侧到根尖的转运，并显著增加了这两种细胞中Cd从根尖到基底外侧的转运。UIC2在llc - ga5 - col150细胞中的作用比在LLC-PK1细胞中的作用更明显。此外，典型的P-gp抑制剂，如环孢素A和阿霉素，在LLC-PK1细胞中略微降低Cd的基底外侧到顶端的运输，而在LLC-GA5-COL 150细胞中则显著降低。这些结果表明，Cd从lc - pk1和lc - ga5 - col 150细胞的顶膜中挤出，可能取决于P-gp的表达水平。2004爱思唯尔爱尔兰有限公司版权所有。
The purpose of this study using LLC-PK1 cells and P-glycoprotein (P-gp) overexpressed LLC-PK1 cells (LLC-GA5-COL 150 cells) was to investigate the secretory transport of cadmium (Cd) via endogenous and overexpressed P-gp, respectively. Cell monolayers cultured on permeable membranes were incubated at 37 degreesC for 60 min with 1 muM CdCl2 from either the apical or the basolateral side. The basolateral-to-apical transport of Cd was 1.7 times higher than the apical-to-basolateral transport of Cd in LLC-GA5-COL 150 cells, while the transport from apical and basolateral sides was almost the same in LLC-PK1 cells. Treatment with a P-gp monoclonal antibody, UIC2, significantly decreased the basolateral-to-apical transport of Cd in LLC-PK1 and LLC-GA5-COL 150 cells, and significantly increased the apical-to-basolateral transport of Cd in both cells. The effects of UIC2 were more marked in LLC-GA5-COL 150 cells than in LLC-PK1 cells. Furthermore, typical P-gp inhibitors such as cyclosporin A, and doxorubicin decreased the basolateral-to-apical transport of Cd slightly in LLC-PK1 cells and significantly in LLC-GA5-COL 150 cells. These results suggest that Cd is extruded from the apical membrane of LLC-PK1 and LLC-GA5-COL 150 cells, probably depending on the level of P-gp expression. (C) 2004 Elsevier Ireland Ltd. All rights reserved.