ATP-DEPENDENT EFFLUX OF CALCEIN BY THE MULTIDRUG-RESISTANCE PROTEIN (MRP) - NO INHIBITION BY INTRACELLULAR GLUTATHIONE DEPLETION
ATP-DEPENDENT EFFLUX OF CALCEIN BY THE MULTIDRUG-RESISTANCE PROTEIN (MRP) - NO INHIBITION BY INTRACELLULAR GLUTATHIONE DEPLETION
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DOI：
10.1016/0014-5793(95)00677-2
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发表时间：
1995-07-17
期刊：
影响因子：
3.5
通讯作者：
PINEDO, HM
中科院分区：
文献类型：
--
作者：
FELLER, N;BROXTERMAN, HJ;PINEDO, HM
在这项研究中，我们报道了多药耐药蛋白(MRP)从肿瘤细胞胞浆转运钙黄绿素，而P-糖蛋白则从胞膜转运钙黄绿素乙氧甲酯。钙黄素在MRP中的转运依赖于ATP，并被丙磺舒和长春新碱所抑制。丁硫氨酸亚磺胺引起的细胞内谷胱甘肽(GSH)耗竭对钙黄素的外流无影响，但可逆转MRP高表达肿瘤细胞柔红霉素蓄积不足。结论：细胞内GSH浓度的大幅降低不会抑制MRP对钙黄素和其他有机阴离子的依赖于ATP的转运，从而抑制MRP对柔红霉素的外流。
In this study we report that the multidrug resistance protein (MRP) transports calcein from the cytoplasmic compartment of tumor cells, in contrast to P-glycoprotein which transports calcein acetoxymethyl ester from the plasmamembrane. The transport of calcein by MRP is ATP-dependent and is inhibited by probenecid and vincristine. Intracellular glutathione (GSH) depletion which occurred when cells vr ere exposed to buthionine sulfoximine had no effect on the efflux of calcein, whereas it reversed the daunorubicin accumulation deficit in MRP overexpressing tumor cells. Tn conclusion, ATP-dependent transport of calcein and possibly other organic anions by MRP is not inhibited by a large decrease of the intracellular GSH concentration, that inhibits daunorubicin efflux by MRP.