Multidrug resistance mediated by the ATP-binding cassette transporter protein MRP.

来自 EBSCO

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摘要：

Resistance to multiple natural product drugs associated with reduced drug accumulation in human tumor cells may be conferred by either the 170 kDa P-glycoprotein or the 190 kDa multidrug resistance protein, MRP. Both MRP and P-glycoprotein belong to the large and ancient ATP-binding cassette (ABC) superfamily of transport proteins but share only 15% amino acid identify. Unlike P-glycoprotein, MRP actively transports conjugated organic anions such as the cysteinyl leukotriene C4 and glutathione-conjugated aflatoxin B1. Transport of unconjugated chemotherapeutic agents appears to require cotransport of glutathione. MRP and several more recently discovered ABC proteins contain an additional NH2-proximal membrane-spanning domain not found in previously characterized ABC transporters. This domain, whose NH2-terminus is extracytosolic, is essential for MRP-mediated transport activity. This review summarizes current knowledge of the structural and transport characteristics of MRP which suggest that the physiologic functions of this protein could range from a protective role in chemical toxicity and oxidative stress to mediation of inflammatory responses involving cysteinyl leukotrienes.

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关键词：

Antineoplastic Agents ABC Transporters Drug Resistance, Multiple multidrug resistance associated protein 抗肿瘤药 ABC转运子抗药性, 多药

DOI：

10.1002/(SICI)1521-1878(199811)20:113.0.CO;2-J

被引量：

1041

年份：

1998