AN ANG1-TIE2-PI3K AXIS IN NEURAL PROGENITOR CELLS INITIATES SURVIVAL RESPONSES AGAINST OXYGEN AND GLUCOSE DEPRIVATION
AN ANG1-TIE2-PI3K AXIS IN NEURAL PROGENITOR CELLS INITIATES SURVIVAL RESPONSES AGAINST OXYGEN AND GLUCOSE DEPRIVATION
复制标题
神经祖细胞中的 ANG1-TIE2-PI3K 轴启动针对缺氧和葡萄糖剥夺的生存反应
DOI：
10.1016/j.neuroscience.2009.01.076
复制
发表时间：
2009-05-05
期刊：
影响因子：
3.3
通讯作者：
Zhang, Y.
中科院分区：
文献类型：
--
作者：
Bai, Y.;Meng, Z.;Zhang, Y.
神经前体细胞（NPCs）具有在脑缺血后存活并参与脑卒中后神经发生的潜能。然而，目前尚不清楚NPC中的生存反应是如何启动的。利用胚胎小鼠NPC和体外氧和葡萄糖剥夺（OGD）模型，我们发现血管生成素-1（Ang 1）可以阻止OGD诱导的NPC凋亡，这一点通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记和annexin V标记得到证实。Ang 1可显著提高图尼卡内膜内皮激酶2（Tie 2）的自磷酸化水平，提示NPC上存在功能性Tie 2受体。OGD条件下的NPC表现出Akt磷酸化减少，Bcl-2/Bax比值降低，caspase-3活化，PARP裂解，β-catenin和nestin下调。Ang 1可逆转上述变化，并显著提高OGD条件下NPC的存活率，但Ang 1的上述作用可被可溶性Tie 2 Fc融合蛋白胞外区（sTie 2Fc）或磷脂酰肌醇3激酶（PI 3 K）抑制剂2-（4-吗啉基）-8-苯基-1（4 H）-苯并吡喃-4-酮（LY 294002）阻断。我们的研究结果表明，存在一个Ang 1-Tie 2-PI 3 K信号轴，这是必不可少的，在启动对脑缺血和缺氧的NPC的生存反应。(C)2009年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Neural progenitor cells (NPCs) have the potential to survive brain ischemia and participate in neurogenesis after stroke. However, it is not clear how survival responses are initiated in NPCs. Using embryonic mouse NPCs and the in vitro oxygen and glucose deprivation (OGD) model, we found that angiopoietin-1 (Ang1) could prevent NPCs from OGD-induced apoptosis, as evidenced by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and annexin V labeling. Ang1 significantly elevated tunica intima endothelial kinase 2 (Tie2) autophosphorylation level, suggesting the existence of functional Tie2 receptors on NPCs. NPCs under OGD conditions exhibited reduction of Akt phosphorylation, decrease of the Bcl-2/Bax ratio, activation of caspase-3, cleavage of PARP, and downregulation of beta-catenin and nestin. Ang1 reversed the above changes concomitantly with significant rising of survival rates of NPCs under OGD, but all these effects of Ang1 could be blocked by either soluble extracellular domain of Tie2 Fc fusion protein (sTie2Fc) or the phosphoinositide 3-kinase (PI3K) inhibitor 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one (LY294002). Our findings suggest the existence of an Ang1-Tie2-PI3K signaling axis that is essential in initiation of survival responses in NPCs against cerebral ischemia and hypoxia. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.