Demonstration and structural comparison of receptors for insulin-like growth factor-I and -II (IGF-I and -II) in brain and blood-brain barrier.

Demonstration and structural comparison of receptors for insulin-like growth factor-I and -II (IGF-I and -II) in brain and blood-brain barrier.
复制标题

大脑和血脑屏障中胰岛素样生长因子-I 和-II(IGF-I 和-II)受体的演示和结构比较。

DOI:
10.1016/0006-291x(87)91618-4
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发表时间:
1987
影响因子:
3.1
通讯作者:
Pardridge,WM
Pardridge,WM
中科院分区:
生物学4区
文献类型:
--
作者:
Rosenfeld,RG;Pham,H;Keller,BT;Borchardt,RT;Pardridge,WM

文献摘要

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通过亲和交联技术和特异性抗受体抗体,鉴定并表征了无微血管大鼠脑细胞膜(RBCM)和构成血脑屏障(BBB)的微血管中胰岛素样生长因子(IGF)I和II的特异性受体。研究了两种不同的 BBB 模型:分离的大鼠脑毛细血管和培养的牛脑微血管内皮细胞。与 125-I-IGF-I 交联,然后进行十二烷基硫酸钠聚丙烯酰胺凝胶电泳 (SDS-PAGE),显示两种 BBB 制剂中的 α 亚基表观 Mr= 138,000,而 RBCM 中的 α 亚基为 120,000。交联被未标记的 IGF 和胰岛素抑制,但不被针对 IGF-II 受体的抗体抑制。当 125-I-IGF-II 交联,然后在还原条件下进行 SDS-PAGE 时,在 RBCM 和两种 BBB 制剂中鉴定出明显的 Mr= 250,000 的主要条带。这条带在大脑和 BBB 膜中以大约相当的 Mr 迁移,被未标记的 IGF 和 IGF-II 受体特异性抗体抑制。因此,大鼠和牛脑微血管都具有经典的 I 型和 II 型 IGF 受体。虽然脑 I 型受体的 α 亚基比 BBB 的小,但脑和 BBB 的 II 型受体在结构和免疫学上似乎相同。
Specific receptors for insulin-like growth factors (IGF) I and II on microvessel-free rat brain cell membranes (RBCM) and in the microvessels that constitute the blood-brain barrier (BBB) were identified and characterized by means of affinity cross-linking techniques and specific anti-receptor antibodies. Two different models of BBB were examined: isolated rat brain capillaries and cultured bovine brain microvessel endothelial cells. Cross-linking with 125-I-IGF-I, followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), revealed an α subunit of apparent Mr= 138,000 in both BBB preparations, compared to 120,000 in RBCM. Cross-linking was inhibited by unlabeled IGF and insulin, but not by antibody directed against the IGF-II receptor. When 125-I-IGF-II was cross-linked, followed by SDS-PAGE under reducing conditions, a major band of apparent Mr= 250,000 was identified in RBCM and both BBB preparations. This band, which migrated with an approximately equivalent Mr in both brain and BBB membranes, was inhibited by unlabeled IGF and by antibody specific for the IGF-II receptor. Thus, both rat and bovine brain microvessels possess classical Type I and II IGF receptors. While the α subunit of the Type I receptor of brain is smaller than that of the BBB, the Type II receptor of brain and BBB appear to be structurally and immunologically identical.