In situ localization of P-glycoprotein (ABCB1) in human and rat brain
In situ localization of P-glycoprotein (ABCB1) in human and rat brain
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DOI：
10.1369/jhc.5a6870.2006
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发表时间：
2006-10-01
影响因子：
3.2
通讯作者：
Bendayan, Moise
中科院分区：
文献类型：
--
作者：
Bendayan, Reina;Ronaldson, Patrick T.;Bendayan, Moise
几种异生物质（包括药物制剂）进出中枢神经系统（CNS）的转运涉及 ATP 依赖性膜结合外排转运蛋白的表达，例如血脑屏障（BBB）上的 P-糖蛋白（P-gp）。先前的研究已经记录了脑微血管内皮细胞中 P-gp 的基因和蛋白质表达。然而，P-gp 的确切定位，特别是在 BBB 的近腔侧，仍然存在争议。在本研究中，我们使用免疫金细胞化学在电子显微镜水平上检查了 P-gp 在大鼠和人脑组织中原位的细胞/亚细胞分布。 P-gp 定位于毛细血管内皮细胞的腔膜和近腔膜以及邻近的周细胞和星形胶质细胞。在亚细胞内，P-gp 沿着核膜、小窝、细胞质小泡、高尔基复合体和粗面内质网 (RER) 分布。这些结果为 P-gp 在人类和啮齿动物脑毛细血管中沿质膜以及蛋白质合成、糖基化和膜运输位点的表达提供了证据。此外，它存在于 BBB 的腔极和近腔极，包括周细胞和星形胶质细胞质膜，表明该糖蛋白可能在细胞和亚细胞水平上调节整个 CNS BBB 中的药物转运过程。
Transport of several xenobiotics including pharmacological agents into or out of the central nervous system (CNS) involves the expression of ATP-dependent, membrane-bound efflux transport proteins such as P-glycoprotein (P-gp) at the blood-brain barrier (BBB). Previous studies have documented gene and protein expression of P-gp in brain microvessel endothelial cells. However, the exact localization of P-gp, particularly at the abluminal side of the BBB, remains controversial. In the present study we examined the cellular/sub-cellular distribution of P-gp in situ in rat and human brain tissues using immunogold cytochemistry at the electron microscope level. P-gp localizes to both the luminal and abluminal membranes of capillary endothelial cells as well as to adjacent pericytes and astrocytes. Sub-cellularly, P-gp is distributed along the nuclear envelope, in caveolae, cytoplasmic vesicles, Golgi complex, and rough endoplasmic reticulum (RER). These results provide evidence for the expression of P-gp in human and rodent brain capillary along their plasma membranes as well as at sites of protein synthesis, glycosylation, and membrane trafficking. In addition, its presence at the luminal and abluminal poles of the BBB, including pericytes and astrocyte plasma membranes, suggests that this glycoprotein may regulate drug transport processes in the entire CNS BBB at both the cellular and subcellular level.