OVEREXPRESSION OF THE GENE ENCODING THE MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN RESULTS IN INCREASED ATP-DEPENDENT GLUTATHIONE S-CONJUGATE TRANSPORT
OVEREXPRESSION OF THE GENE ENCODING THE MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN RESULTS IN INCREASED ATP-DEPENDENT GLUTATHIONE S-CONJUGATE TRANSPORT
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DOI：
10.1073/pnas.91.26.13033
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发表时间：
1994-12-20
影响因子：
11.1
通讯作者：
JANSEN, PLM
中科院分区：
文献类型：
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作者：
MULLER, M;MEIJER, C;JANSEN, PLM
多药耐药相关蛋白（MRP）是一种分子量为180- 195 kDa的糖蛋白，与人类肿瘤细胞的多药耐药相关。MRP主要位于质膜上，通过将天然产物药物输出到细胞外而产生耐药性。在这里，我们证明了MRP基因在人类癌细胞中的过度表达增加了从这些细胞中分离的质膜囊泡中ATP依赖性谷胱甘肽S-缀合物载体的活性。已知谷胱甘肽S缀合物输出载体介导二价阴离子缀合物从哺乳动物细胞中的排泄，并且被认为在缀合的外源性物质的消除中起作用。我们的研究结果表明，MRP可以通过促进来自细胞的药物修饰产物的专家而引起多药耐药，并且他们揭示了耐药性与细胞谷胱甘肽和谷胱甘肽S-转移酶水平之间的联系。
The multidrug resistance-associated protein (MRP) is a 180- to 195-kDa glycoprotein associated with multidrug resistance of human tumor cells. MRP is mainly located in the plasma membrane and it confers resistance by exporting natural product drugs out of the cell. Here we demonstrate that overexpression of the MRP gene in human cancer cells increases the ATP-dependent glutathione S-conjugate carrier activity in plasma membrane vesicles isolated from these cells. The glutathione S conjugate export carrier is known to mediate excretion of bivalent anionic conjugates from mammalian cells and is thought to play a role in the elimination of conjugated xenobiotics. Our results suggest that MRP can cause multidrug resistance by promoting the expert of drug modification products from cells and they shed light on the reported link between drug resistance and cellular glutathione and glutathione S-transferase levels.