Hypoxia induces the activation of the phosphatidylinositol 3-kinase/Akt cell survival pathway in PC12 cells -: Protective role in apoptosis
Hypoxia induces the activation of the phosphatidylinositol 3-kinase/Akt cell survival pathway in PC12 cells -: Protective role in apoptosis
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DOI：
10.1074/jbc.m011688200
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发表时间：
2001-06-22
影响因子：
4.8
通讯作者：
del Peso, L
中科院分区：
文献类型：
--
作者：
Alvarez-Tejado, M;Naranjo-Suárez, S;del Peso, L
缺氧是一种常见的环境应激，影响信号通路和细胞功能。包括神经内分泌嗜铬细胞在内的几种细胞类型已经进化为感知氧气水平并启动对缺氧的特定适应性反应。在这里，我们报告，在缺氧条件下，大鼠嗜铬细胞瘤PC 12细胞对血清戒断和化疗诱导的凋亡有抵抗力。在用去铁胺（一种模拟缺氧的许多作用的化合物）处理后也观察到这种作用。缺氧依赖性的细胞凋亡保护与磷脂酰肌醇3-激酶（PI 3 K）/Akt途径的激活相关，其在缺氧或去铁胺处理3-4小时后检测到，并且在维持缺氧条件的同时持续。缺氧诱导的Akt活化可以通过放线菌酮或放线菌素D处理来防止，这表明需要从头蛋白质合成。最后，PI 3 K的抑制损害了对细胞凋亡的保护和响应缺氧的Akt的激活，表明这两种现象之间的功能联系。因此，降低的氧张力通过激活PI 3 K/Akt存活途径调节PC 12细胞的凋亡。
Hypoxia is a common environmental stress that influences signaling pathways and cell function. Several cell types, including neuroendocrine chromaffin cells, have evolved to sense oxygen levels and initiate specific adaptive responses to hypoxia. Here we report that under hypoxic conditions, rat pheochromocytoma PC12 cells are resistant to apoptosis induced by serum withdrawal and chemotherapy treatment. This effect is also observed after treatment with deferoxamine, a compound that mimics many of the effects of hypoxia, The hypoxia-dependent protection from apoptosis correlates with activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, which is detected after 3-4 h of hypoxic or deferoxamine treatment and is sustained while hypoxic conditions are maintained. Hypoxia-induced Akt activation can be prevented by treatment with cycloheximide or actinomycin D, suggesting that de novo protein synthesis is required. Finally, inhibition of PI3K impairs both the protection against apoptosis and the activation of Akt in response to hypoxia, suggesting a functional link between these two phenomena. Thus, reduced oxygen tension regulates apoptosis in PC12 cells through activation of the PI3K/Akt survival pathway.