کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10468408 926177 2005 17 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Localization of Brain Endothelial Luminal and Abluminal Transporters with Immunogold Electron Microscopy
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی عصب شناسی
پیش نمایش صفحه اول مقاله
Localization of Brain Endothelial Luminal and Abluminal Transporters with Immunogold Electron Microscopy
چکیده انگلیسی
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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: NeuroRX - Volume 2, Issue 1, January 2005, Pages 27-43
نویسندگان
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