MODULATION OF BLOOD-BRAIN BARRIER NUTRIENT TRANSPORT

血脑屏障(BBB)GLUT1葡萄糖转运体在 脑内，定位于毛细血管内皮细胞。人血清白蛋白的体外研究 葡萄糖转运蛋白的其他异构体已经证明 葡萄糖转运的上调是通过转位 将蛋白质从细胞内转运到细胞外 膜，即转运体招募。下调监管是 特点是运输机被重新安置到内部地点。它 被提议在体内实验操作血脑屏障葡萄糖转运体 (确认已实现快速上调或下调监管)，以及 然后研究GLUT1转运蛋白的定位模式 免疫金电镜法。BBB的一个独特功能 血管内皮细胞是GLUT1转运体的明显不对称分布； 肾小管膜上的转运蛋白数量是 腔膜，距离相对较短(300-500 nm) 分离这些内皮细胞表面。因为管腔毛细血管 膜被认为是血脑屏障葡萄糖的限速部位 运输可能发生，我们还建议检验假设，快速 这些内皮细胞的上调和下调可能不仅涉及 细胞质转运蛋白的移位，但也从 阴囊到腔膜的距离相对较短。 使用膜封闭剂，在体内选择性地进行实验 操作腔膜GLUT1转运蛋白是计划的。它是 预计这项工作将提供对细胞 血脑屏障葡萄糖转运的机制，并定义转运蛋白的反应 缺氧、脑损伤、癫痫发作和脑肿瘤。

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.