MODULATION OF BLOOD-BRAIN BARRIER NUTRIENT TRANSPORT

血脑屏障（BBB）GLUT 1葡萄糖转运蛋白在脑组织中含量丰富。 脑，并定位于毛细血管内皮。 的体外研究 葡萄糖转运蛋白的其它同种型已经证明， 葡萄糖转运的上调是通过 从细胞内位点到细胞外的转运蛋白 膜，即，运输员招募 下调是 其特点是运输者搬迁到内部地点。 它 拟在体内实验性操纵血脑屏障葡萄糖转运蛋白 (to确认已实现快速上调或下调），以及 然后研究GLUT 1转运蛋白的定位模式， 免疫金电镜法。 BBB的独特功能 内皮细胞是GLUT 1转运蛋白的明显不对称分布; 腔外膜的转运蛋白的数量比腔外膜的转运蛋白的数量多3-4倍。 管腔膜，和相对短的距离（300-500 nm） 分离这些内皮表面。 因为腔内毛细血管 膜被认为是血脑屏障葡萄糖的速率限制的位点， 运输可能发生，我们还建议测试假设，快速 这些内皮细胞的上调和下调可能不仅涉及 细胞质转运蛋白的易位，但也从 跨相对短的距离的外腔到腔膜。 使用膜不渗透剂，位点选择性体内实验 计划操纵内腔膜GLUT 1转运蛋白。 是 预计这项工作将提供深入了解细胞 BBB葡萄糖转运的机制，并定义转运蛋白的反应， 缺氧、脑损伤、癫痫和脑肿瘤。

The blood-brain barrier (BBB) GLUT1 glucose transporter is abundant in brain, and localized to the capillary endothelia. In vitro studies of other isoforms of the glucose transporter have demonstrated that rapid up-regulation of glucose transport is achieved through translocation of transporter proteins from intracellular sites to the external cell membrane, i.e., transporter recruitment. Down-regulation is characterized by relocation of the transporters to internal sites. It is proposed to experimentally manipulate BBB glucose transporter in vivo (to confirm that rapid up- or down regulation has been achieved), and then study the localization patterns of the GLUT1 transporter using immunogold electron microscopic methods. A unique feature of BBB endothelia is the apparent asymmetric distribution of GLUT1 transporters; ablumenal membranes have a 3-4 fold greater number of transporters than the lumenal membrane, and relatively short distances (300-500 nm) separate these endothelial surfaces. Because the lumenal capillary membrane is believed to be the site where rate-limitation of BBB glucose transport may occur, we also propose to test the hypothesis that rapid up-and down-regulation in these endothelia may not only involve translocation of cytoplasmic transporter proteins, but also movement from the ablumenal to lumenal membrane across relatively short distances. Using membrane-impermeant agents, site-selective in vivo experimental manipulation of lumenal membrane GLUT1 transporters is planned. It is anticipated that this work will provide insights into the cellular mechanisms of BBB glucose transport, and define transporter responses in anoxia, brain injury, seizures and in brain tumors.