Localization of brain endothelial luminal and abluminal transporters with immunogold electron microscopy

被引：85

作者：

Cornford E.M. ^{[1
,2
,3
,4
]}

Hyman S. ^{[2
]}

机构：

[1] Vet. Admin. Gtr. Los Angeles H., Los Angeles

[2] Department of Neurology, UCLA School of Medicine, Los Angeles

[3] Brain Research Institute, UCLA School of Medicine, Los Angeles

[4] W127 Neurology, Vet. Aff. Gtr. Los Angeles H., Los Angeles, CA 90073

来源：

NeuroRX | 2005年 / 2卷 / 1期

基金：

美国国家卫生研究院;

关键词：

Aquaporin-4; Blood-brain barrier; Caveolin-1; Claudin-5; Electron microscopy; GFAP; GLUT1 glucose transporter; Occludin; Pegylated immunoliposome;

D O I：

10.1602/neurorx.2.1.27

中图分类号：

学科分类号：

摘要：

Immunogold electron microscopy has identified a variety of blood-brain barrier (BBB) proteins with transporter and regulatory functions. For example, isoforms of the glucose transporter, protein kinase C (PKC), and caveolin-1 are BBB specific. Isoform 1 of the facilitative glucose transporter family (GLUT1) is expressed solely in endothelial (and pericyte) domains, and ∼75% of the protein is membrane-localized in humans. Evidence is presented for a water cotransport function of BBB GLUT1. A shift in transporter polarity characterized by increased luminal membrane GLUT1 is seen when BBB glucose transport is upregulated; but a greater abluminal membrane density is seen in the human BBB when GLUT1 is downregulated. PKC colocalizes with GLUT1 within these endothelial domains during up- and downregulation, suggesting that a PKC-mediated mechanism regulates human BBB glucose transporter expression. Occludin and claudin-5 (like other tight-junctional proteins) exhibit a restricted distribution, and are expressed solely within interendothelial clefts of the BBB. GFAP (glial fibrillary acidic protein) is uniformly expressed throughout the foot-processes and the entire astrocyte. But the microvascular-facing membranes of the glial processes that contact the basal laminae are also polarized, and their transporters may also redistribute within the astrocyte. Monocarboxylic acid transporter and water channel (Aquaporin-4) expression are enriched at the glial foot-process, and both undergo physiological modulation. We suggest that as transcytosis and efflux mechanisms generate interest as potential neurotherapeutic targets, electron microscopic confirmation of their site-specific expression patterns will continue to support the CNS drug discovery process.

引用

页码：27 / 43

页数：16

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