HUMAN BLOOD-BRAIN-BARRIER TRANSFERRIN RECEPTOR

HUMAN BLOOD-BRAIN-BARRIER TRANSFERRIN RECEPTOR
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DOI:
10.1016/0026-0495(87)90099-0
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发表时间:
1987-09-01
影响因子:
9.8
通讯作者:
JING, Y
JING, Y
中科院分区:
医学1区
文献类型:
--
作者:
PARDRIDGE, WM;EISENBERG, J;JING, Y

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以人血脑屏障为模型,研究了~(125)I-人全转铁蛋白在离体人脑毛细血管中的结合和内吞动力学。人脑毛细血管的肽的结合和内吞是温度依赖性的,并且结合被全转铁蛋白饱和,但不是由胰岛素,生长抑素,或加压素。结合反应的Scatchard分析揭示了解离常数为448 ± 100。110 ng/mL(5.6 ±. 1.4 nmol/L),最大结合常数(R 0)为8.0 ± 0.01。1.5 ng/mg蛋白质。因此,BBB转铁蛋白受体的亲和力和能力与BBB受体对胰岛素、胰岛素样生长因子-I或胰岛素样生长因子-II的亲和力和能力在相同的数量级内。人脑毛细血管转铁蛋白受体也检测到小鼠单克隆抗体的受体,使用亲和素/生物素/过氧化物酶技术。总之,这些研究表征了人血脑屏障转铁蛋白受体,并支持该受体作为转运系统介导转铁蛋白结合铁通过人脑毛细血管内皮细胞的转胞吞作用的假设。
The kinetics of binding and endocytosis of 125I-human holotransferrin by isolated human brain capillaries was examined using this system as a model of the human blood-brain barrier (BBB). Both binding and endocytosis of the peptide by human brain capillaries was temperature-dependent and the binding was saturated by holotransferrin, but not by insulin, somatostatin, or vasopressin. Scatchard analysis of the binding reaction revealed a dissociation constant of 448 .+-. 110 ng/mL (5.6 .+-. 1.4 nmol/L) and a maximal binding constant (R0) of 8.0 .+-. 1.5 ng/mg protein. Thus, the affinity and capacity of the BBB transferrin receptor is within the same order of magnitude as the affinity and capacity of the BBB receptors for insulin, insulinlike growth factor-I, or insulinlike growth factor-II. The human brain capillary transferrin receptor was also detected with a mouse monoclonal antibody to the receptor using the avidin/biotin/peroxidase technique. In conclusion, these studies characterize the human BBB transferrin receptor and support the hypothesis that this receptor acts as a transport system which mediates the transcytosis of transferrin-bound iron through the brain capillary endothelial cell in man.