Angiopoietin-1 inhibits endothelial cell apoptosis via the Akt/survivin pathway
Angiopoietin-1 inhibits endothelial cell apoptosis via the Akt/survivin pathway
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DOI：
10.1074/jbc.275.13.9102
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发表时间：
2000-03-31
影响因子：
4.8
通讯作者：
Sessa, WC
中科院分区：
文献类型：
--
作者：
Papapetropoulos, A;Fulton, D;Sessa, WC
有效的血管生成反应必须与内皮细胞的生存机制相结合，以保持新形成血管的完整性。血管生成素-1（Ang-I）是胚胎血管稳定、分支形态发生和出生后血管生成所必需的内皮特异性配体，但其对内皮细胞存活的贡献尚未完全阐明。在这里，我们表明Ang-l通过Tie 2受体起作用，诱导存活的丝氨酸-苏氨酸激酶Akt（或蛋白激酶B）的磷酸化。这与内皮细胞中凋亡抑制剂生存素的上调和保护内皮免受死亡诱导刺激有关。此外，显性失活的存活素否定了Ang-I保护细胞免于经历凋亡的能力。在内皮细胞中由Akt和存活素介导的抗凋亡途径的激活可能有助于体内血管生成期间血管结构的Ang-I稳定。
A productive angiogenic response must couple to the survival machinery of endothelial cells to preserve the integrity of newly formed vessels. Angiopoietin-1 (Ang-l) is an endothelium-specific ligand essential for embryonic vascular stabilization, branching morphogenesis, and post-natal angiogenesis, but its contribution to endothelial cell survival has not been completely elucidated. Here we show that Ang-l acting via the Tie 2 receptor induces phosphorylation of the survival serine-threonine kinase, Akt (or protein kinase B). This is associated with up-regulation of the apoptosis inhibitor, survivin, in endothelial cells and protection of endothelium from death-inducing stimuli. Moreover, dominant negative survivin negates the ability of Ang-l to protect cells from undergoing apoptosis, The activation of antiapoptotic pathways mediated by Akt and survivin in endothelial cells may contribute to Ang-l stabilization of vascular structures during angiogenesis, in vivo.