Induction of vascular endothelial growth factor receptors and phosphatidylinositol 3′-kinase/Akt signaling by global cerebral ischemia in the rat

Induction of vascular endothelial growth factor receptors and phosphatidylinositol 3′-kinase/Akt signaling by global cerebral ischemia in the rat
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DOI:
10.1016/s0306-4522(00)00331-6
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发表时间:
2000-01-01
期刊:
影响因子:
3.3
通讯作者:
Greenberg, DA
Greenberg, DA
中科院分区:
医学3区
文献类型:
--
作者:
Jin, KL;Mao, XO;Greenberg, DA

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血管内皮生长因子是一种血管生成肽,其与靶细胞上的酪氨酸激酶受体结合以激活涉及磷脂酰肌醇3 '-激酶和丝氨酸-苏氨酸蛋白激酶Akt的信号转导途径。为了确定这种信号通路是否在脑缺血中被激活,我们检测了大鼠短暂性全脑缺血后大脑皮层和海马中血管内皮生长因子受体1和2以及磷脂酰肌醇3 '-激酶激活的磷酸化Akt的表达。蛋白质印迹分析和免疫细胞化学证实诱导血管内皮生长因子受体1和2的表达,以及抗磷脂酰肌醇3 '-激酶免疫沉淀的磷酸化Akt,结果表明,缺血15分钟后再灌注4-72小时,血管内皮生长因子受体和受体-在体内缺血脑中诱导了偶联的信号转导通路,因此可能参与缺血的内源性神经保护反应。(C)2000 IBRO。由爱思唯尔科技有限公司出版。保留所有权利。
Vascular endothelial growth factor is an angiogenic peptide that binds to tyrosine kinase receptors on target cells to activate signal transduction pathways involving phosphatidylinositol 3'-kinase and the serine-threonine protein kinase, Akt. To determine whether this signaling pathway is activated in cerebral ischemia, we examined the expression of vascular endothelial growth factor receptors 1 and 2, and phosphatidylinositol 3'-kinase-activated phospho-Akt, in the cerebral cortex and hippocampus following transient global cerebral ischemia in the rat. Western blot analysis and immunocytochemistry demonstrated induction of vascular endothelial growth factor receptor 1 and 2 expression, and of anti-phosphatidylinositol 3'-kinase-immunoprecipitated phospho-Akt, in vulnerable regions of the cortex and hippocampus after 15 min of global ischemia acid 4-72 h of reperfusion.These findings demonstrate that vascular endothelial growth factor receptors and receptor-coupled signal transduction pathways are induced in ischemic brain in vivo, and could therefore participate in endogenous neuroprotective responses to ischemia. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved.