Expression of members of the multidrug resistance protein family in human term placenta
Expression of members of the multidrug resistance protein family in human term placenta
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DOI：
10.1152/ajpregu.2000.279.4.r1495
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发表时间：
2000-10-01
影响因子：
2.8
通讯作者：
Marin, JJG
中科院分区：
文献类型：
--
作者：
St-Pierre, MV;Serrano, MA;Marin, JJG
胎盘在一定程度上是一种屏障，可以将有害物质排除在胎儿之外。在人类中，由极化的滋养层细胞和胎儿毛细血管内皮细胞组成的单层合体将母体和胎儿的循环分开。P-糖蛋白在整个妊娠期间存在于合体滋养层细胞中，这与限制胎儿暴露于疏水性和阳离子外源生物的保护作用一致。我们研究了多药耐药蛋白(MRP)家族成员是否在足月胎盘中表达。通过对胎盘cDNA文库的筛选，获得了MRP1、MRP2和MRP3的部分克隆。免疫荧光和免疫印迹研究表明，MRP2定位于顶端合体滋养层细胞膜。MRP1和MRP3主要在血管内皮细胞中表达，在顶端合体滋养层细胞中也有表达。在顶端合体滋养层细胞膜上，阴离子底物二硝基苯基-谷胱甘肽和雌二醇-17-β-葡萄糖醛酸苷的转运也依赖于ATP。鉴于这些转运体的细胞分布，我们假设MRP亚型有助于保护胎儿血液免受有机阴离子的进入，并促进谷胱甘肽/葡萄糖醛酸代谢物在母体循环中的排泄。
The placenta serves, in part, as a barrier to exclude noxious substances from the fetus. In humans, a single-layered syncytium of polarized trophoblast cells and the fetal capillary endothelium separate the maternal and fetal circulations. P-glycoprotein is present in the syncytiotrophoblast throughout gestation, consistent with a protective role that limits exposure of the fetus to hydrophobic and cationic xenobiotics. We have examined whether members of the multidrug resistance protein (MRP) family are expressed in term placenta. After screening a placenta cDNA library, partial clones of MRP1, MRP2, and MRP3 were identified. Immunofluorescence and immunoblotting studies demonstrated that MRP2 was localized to the apical syncytiotrophoblast membrane. MRP1 and MRP3 were predominantly expressed in blood vessel endothelia with some evidence for expression in the apical syncytiotrophoblast. ATP-dependent transport of the anionic substrates dinitrophenyl-glutathione and estradiol-17-beta-glucuronide was also demonstrated in apical syncytiotrophoblast membranes. Given the cellular distribution of these transporters, we hypothesize that MRP isoforms serve to protect fetal blood from entry of organic anions and to promote the excretion of glutathione/glucuronide metabolites in the maternal circulation.