Xenobiotic transport differences in mouse mesangial cell clones expressing mdr1 and mdr3.
Xenobiotic transport differences in mouse mesangial cell clones expressing mdr1 and mdr3.
复制标题
表达 mdr1 和 mdr3 的小鼠系膜细胞克隆中的异生素转运差异。
DOI：
10.1152/ajpcell.1996.270.3.c910
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Bello-Reuss,E
中科院分区：
文献类型：
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作者：
Ernest,S;Bello-Reuss,E
P-糖蛋白（PGP）赋予癌细胞多药耐药性，在小鼠肾近曲小管和系膜中表达。我们报告了系膜细胞中 PGP 的表达及其外源物质转运功能。研究在小鼠系膜细胞系 (TKGM) 和两个细胞克隆中进行。核糖核酸酶保护测定和蛋白质印迹分析表明，TKGM 细胞表达 mdr1 和 mdr3，这是导致多药耐药性的亚型。 TKGM-F12 细胞共表达 mdr1 和 mdr3，而 TKGM-G2 细胞仅表达 mdr1。通过罗丹明 123 (R-123) 流出量测量的药物转运功能在 TKGM-F12 中比在 TKGM-G2 细胞中小。 PGP 底物阿霉素、环孢素 A、长春花碱和维拉帕米抑制 TKGM 和 TKGM-G2 细胞中的 R-123 转运。在所研究的细胞中，PGP 赋予了对阿霉素一定程度的耐药性；同时接触阿霉素和另一种 PGP 底物会损害细胞生长。小鼠系膜细胞克隆中 mdr1 和 mdr3 的差异表达、mdr1 PGP 转运 R-123 的能力以及共表达 mdr1 和 mdr3 产物的 TKGM-F12 细胞中 PGP 介导的转运受损。 PGP 可能在系膜细胞中发挥生理作用。
P-glycoprotein (PGP), which confers multidrug resistance to cancer cells, is expressed in mouse kidney proximal tubule and mesangium. We report on the expression of PGP and its xenobiotic transport function in mesangial cells. Studies were performed in a mouse mesangial cell line (TKGM) and two cell clones. Ribonuclease protection assay and Western blot analysis demonstrated that TKGM cells expressed mdr1 and mdr3, the isoforms responsible for multidrug resistance. TKGM-F12 cells coexpressed mdr1 and mdr3 whereas TKGM-G2 cells expressed only mdr1. The drug transport function, measured by rhodamine 123 (R-123) efflux, was smaller in TKGM-F12 than in TKGM-G2 cells. The PGP substrates adriamycin, cyclosporin A, vinblastine, and verapamil inhibited R-123 transport in TKGM and TKGM-G2 cells. In the cells studied, PGP conferred some resistance to adriamycin; concomitant exposure to adriamycin with another PGP substrate impaired cell growth. The differential expression of mdr1 and mdr3 in mouse mesangial cell clones, the ability of mdr1 PGP to transport R-123, and the impairment of PGP-mediated transport in TKGM-F12 cells, coexpressing mdr1 and mdr3 products, are demonstrated. PGP may play a physiological role in mesangial cells.