ATP-dependent transport of glutathione S-conjugates by the multidrug resistance-associated protein.

ATP-dependent transport of glutathione S-conjugates by the multidrug resistance-associated protein.
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发表时间:
1994-09
期刊:
影响因子:
11.2
通讯作者:
G. Jedlitschky;I. Leier;U. Buchholz;M. Center;D. Keppler
G. Jedlitschky;I. Leier;U. Buchholz;M. Center;D. Keppler
中科院分区:
医学1区
文献类型:
--
作者:
G. Jedlitschky;I. Leier;U. Buchholz;M. Center;D. Keppler

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内源性谷胱甘肽结合物白三烯C4(LTC 4)的ATP依赖性转运在从过表达多药耐药相关蛋白的人白血病细胞(HL 60/ADR)制备的膜囊泡中比从药物敏感的亲本HL 60细胞或回复突变细胞高25倍以上。以S-(2,4-二硝基苯基)谷胱甘肽为底物得到了类似的结果。光亲和标记在HL 60/ADR膜中优先检测到190千道尔顿的蛋白结合[3 H] LTC 4和8-叠氮基[alpha-32 P]ATP。[3 H] LTC 4标记的190千道尔顿的蛋白质免疫沉淀的抗血清对多药耐药相关蛋白的COOH-末端序列。我们的研究结果表明,多药耐药相关蛋白介导的LTC 4和结构相关的阴离子两亲性共轭物的ATP依赖性运输。
The ATP-dependent transport of the endogenous glutathione conjugate leukotriene C4 (LTC4) was more than 25-fold higher in membrane vesicles prepared from human leukemia cells (HL60/ADR) overexpressing the multidrug resistance-associated protein than from drug-sensitive parental HL60 cells or revertant cells. Similar results were obtained with S-(2,4-dinitrophenyl)glutathione as substrate. Photoaffinity labeling detected preferentially in the HL60/ADR membranes a 190-kilodalton protein binding [3H]LTC4 and 8-azido[alpha-32P]ATP. The [3H]LTC4-labeled 190-kilodalton protein was immunoprecipitated by an antiserum against the COOH-terminal sequence of multidrug resistance-associated protein. Our results indicate that multidrug resistance-associated protein mediates the ATP-dependent transport of LTC4 and structurally related anionic amphiphilic conjugates.