Multidrug resistance-associated protein2 (MRP2) plays an important role in the biliary excretion of glutathione conjugates of 4-hydroxynonenal
Multidrug resistance-associated protein2 (MRP2) plays an important role in the biliary excretion of glutathione conjugates of 4-hydroxynonenal
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DOI：
10.1016/s0891-5849(02)00906-1
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发表时间：
2002-08-01
影响因子：
7.4
通讯作者：
Horie, T
中科院分区：
文献类型：
--
作者：
Ji, B;Ito, K;Horie, T
4-羟基-反式-2，3-壬烯醛（HNE）的谷胱甘肽（GSH）结合物是脂质过氧化的终产物。在本研究中，使用表达人多药耐药相关蛋白2（MRP 2）的Madin-Darby犬肾11（MDCK 11）细胞在体外研究了多药耐药相关蛋白2（MRP 2）在HNE（HNE-SG）GSH结合物胆汁排泄中的作用，并使用MRP 2表达缺陷的突变大鼠品系（高胆红素血症大鼠[EHBR]）在体内研究了MRP 2。开发了一种高效液相色谱法来测定HNE-SG结合物。该方法可分离四种非对映异构体HNE-SG偶联物。用FINE孵育细胞单层后，可检测到4种HNE-SG结合物中的3种。人MRP 2的表达导致HNE-SG缀合物通过MDCK 11细胞顶膜的排泄增加10倍。静脉注射HNE后，四种HNE-SG结合物在Sprague道利大鼠胆汁中迅速出现，而在EHBR胆汁中未检测到HNE-SG结合物。这些结果证明了MRP 2在HNE-SG缀合物的胆汁排泄中的作用。(C)2002年爱思唯尔科学公司
Glutathione (GSH) conjugates of 4-hydroxy-trans-2,3-nonenal (HNE) are the final products of lipid peroxidation. In the present study, the role of multidrug resistance-associated protein 2 (MRP2) in biliary excretion of GSH conjugates of HNE (HNE-SG) was studied in vitro by using Madin-Darby canine kidney 11 (MDCK 11) cells expressing human MRP2 and in vivo using a mutant rat strain whose MRP2 expression is defective (Eisai-hyperbilirubinemic rats [EHBR]). A high-performance liquid chromatography method was developed to assay HNE-SG conjugates. Four diastereomeric HNE-SG conjugates could be separated with this method. Three of four HNE-SG conjugates were detectable after incubation of the cell monolayers with FINE. Expression of human MRP2 resulted in a 10-fold increase in HNE-SG conjugates excretion across the apical membrane of MDCK 11 cells. The four HNE-SG conjugates appeared swiftly in bile from Sprague Dawley rats after intravenous administration of HNE, whereas no detectable HNE-SG conjugates were observed in the bile of EHBR. These results demonstrate the role of MRP2 in the biliary excretion of HNE-SG conjugates. (C) 2002 Elsevier Science Inc.