Expression of P-glycoprotein in human cerebral cortex microvessels
Expression of P-glycoprotein in human cerebral cortex microvessels
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DOI：
10.1177/002215540205001212
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发表时间：
2002-12-01
影响因子：
3.2
通讯作者：
Bertossi, M
中科院分区：
文献类型：
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作者：
Virgintino, D;Robertson, D;Bertossi, M
P-糖蛋白(P-gp)是一种依赖于ATP的外排转运蛋白，能从细胞中排出非极性分子，包括细胞毒物质和药物。它最初是在癌细胞中发现的，后来被证明是工作在血脑屏障(BBB)的复杂运输系统的正常组成部分。以往的研究表明，在脑内，P-gp定位于血脑屏障内皮细胞的管腔质膜上，它可能与这些细胞的腔室相互作用。本研究的目的是原位确定P-gp在人脑中的细胞表达部位，并从形态上确定P-gp与小窝框架的结构和功能蛋白小窝蛋白-1之间是否存在关联。这项研究是用免疫共聚焦显微镜在人脑皮质上进行的，P-gp和小窝蛋白-1都有抗体。结果表明，P-gp标记皮质的微血管，转运蛋白定位于腔内皮质室，在那里它与小窝蛋白-1共定位。P-gp与小窝蛋白-1共定位的证明为P-gp/小窝蛋白-1关系的生化研究提供了形态支持，并使我们认为这些分子之间的相互作用可能发生在血脑屏障内皮细胞。
P-Glycoprotein (P-gp) is an ATP-dependent efflux transporter that extrudes non-polar molecules, including cytotoxic substances and drugs, from the cells. It was initially found in cancer cells and then was shown to be a normal component of complex transport systems working at the blood-brain barrier (BBB). Previous studies have demonstrated that, in the brain, P-gp is localized on the luminal plasmalemma of BBB endothelial cells and that it may interact with the caveolar compartment of these cells. The aim of this study was to identify the site of cellular expression of P-gp in human brain in situ and to morphologically determine whether an association may exist between P-gp and caveolin-1, a structural and functional protein of the caveolar frame. The study was carried out on human cerebral cortex by immunoconfocal microscopy with antibodies to both P-gp and caveolin-1. The results show that P-gp marks the microvessels of the cortex and that the transporter is localized in the luminal endothelial compartment, where it co-localizes with caveolin-1. The demonstration of this co-localization of P-gp with caveolin-1 contributes a morphological backing to biochemical studies on P-gp/caveolin-1 relationships and leads us to suggest that interactions between these molecules may occur at the BBB endothelia.