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首页> 外文期刊>Advances in enzyme regulation >Export pumps for anionic conjugates encoded by MRP genes.
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Export pumps for anionic conjugates encoded by MRP genes.

机译：MRP基因编码的阴离子共轭物的出口泵。

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Several members of the multidrug resistance protein (MRP) family mediate the ATP-dependent transport of amphiphilic anions across membranes. The substrate specificity of recombinant human MRP1 has been most extensively defined by use of inside-out membrane vesicles. Substrates include the glutathione S-conjugate leukotriene C4, 17 beta-glucuronosyl estradiol, glucuronosyl bilirubin, glutathione disulfide, in addition to the fluorescent lipophilic anion Fluo-3. These substances are also substrates for the apical isoform MRP2, also termed canalicular multispecific organic anion transporter, cMOAT, which shares only 49% amino acid sequence identity with MRP1. The K(m) of leukotriene C4 for MRP2 is 10-fold higher than for MRP1, and the K(m) of 17 beta-glucuronosyl estradiol is 4.8-fold higher for MRP2 than for recombinant human MRP1. Human as well as rat MRP2 confer multidrug resistance to polarized MDCKII cells permanently expressing the recombinant glycoprotein in their apical plasma membrane. Resistance of cells transfected with human and rat MRP2 to etoposide was enhanced 5-fold and 3.8-fold, and resistance to vincristine was enhanced 2.3-fold and 6.0-fold, respectively. Conjugate-transporting members of the MRP family with a related sequence and a similar function have been detected recently. In addition to several MRP isoforms (MRP1-6) and orthologs in mammals (human, rat, rabbit, mouse), MRP family members have been identified in the nematode Caenorhabditis elegans, in the yeast Saccharomyces cerevisiae, and in the plant Arabidopsis thaliana. These conjugate export pumps of the MRP family play a widespread role in detoxification, drug resistance, and, because of the role in the export of glutathione disulfide by MRP1 and MRP2, in the defense against oxidative stress.
机译：多药抗性蛋白（MRP）家族的几个成员介导两性阴离子跨膜的ATP依赖性转运。重组人MRP1的底物特异性已通过使用由内而外的膜囊泡进行了最广泛的定义。底物除了荧光亲脂性阴离子Fluo-3外，还包括谷胱甘肽S共轭白三烯C4、17β-葡萄糖醛糖基雌二醇，葡萄糖醛糖基胆红素，谷胱甘肽二硫化物。这些物质还是根尖异构体MRP2（也称为小管多特异性有机阴离子转运蛋白，cMOAT）的底物，与MRP1仅共享49％的氨基酸序列同一性。 MRP2的白三烯C4的K（m）比MRP1高10倍，而17β-葡萄糖醛糖基雌二醇的K（m）比重组人MRP1高4.8倍。人和大鼠MRP2赋予极化的MDCKII细胞多药耐药性，该细胞在其顶质膜中永久表达重组糖蛋白。用人和大鼠MRP2转染的细胞对依托泊苷的抗性分别提高了5倍和3.8倍，对长春新碱的抗性分别提高了2.3倍和6.0倍。最近已检测到具有相关序列和类似功能的MRP家族的结合转运成员。除了哺乳动物（人类，大鼠，兔子，小鼠）的几种MRP亚型（MRP1-6）和直系同源物外，还在线虫秀丽隐杆线虫，酿酒酵母和拟南芥植物中鉴定了MRP家族成员。 MRP系列的这些共轭输出泵在排毒，抗药性中起着广泛的作用，并且由于MRP1和MRP2在谷胱甘肽二硫化物的输出中起着抵御氧化应激的作用。

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