...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Oncogene >Ionizing radiation induces apoptosis and inhibits neuronal differentiation in rat neural stem cells via the c-Jun NH2-terminal kinase (JNK) pathway
【24h】

Ionizing radiation induces apoptosis and inhibits neuronal differentiation in rat neural stem cells via the c-Jun NH2-terminal kinase (JNK) pathway

机译：电离辐射通过c-Jun NH2-末端激酶（JNK）途径诱导大鼠神经干细胞凋亡并抑制神经元分化

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

A substantial number of neural stem cells (NSCs) continue to proliferate and generate neurons in the central nervous system throughout life. Ionizing radiation, an important adjuvant therapy for glioma patients, may damage NSCs and cause neuronal deficits, such as cognitive dysfunction and memory impairment. However, the precise mechanism of radiation effects on death and differentiation of NSCs remains largely unknown. Here, we found that radiation induced apoptosis in NSCs via the mitochondrial pathway, upregulating the ratio of Bax to Bcl-2 and releasing cytochrome c into the cytoplasm. Radiation also inhibited neuronal differentiation of NSCs by 50%. Of the three stress-associated mitogen-activated protein kinases (MAPKs), only c-Jun NH2-terminal kinase (JNK) was activated in NSCs after radiation. Interestingly, JNK inhibition by the specific inhibitor SP600125 rescued NSCs from apoptosis and improved neuronal differentiation. Furthermore, we examined whether radiation directly inhibits neuronal differentiation or not. Radiation did not affect the promoter activity of NeuroD, a basic helix–loop–helix transcription factor that regulates the expression of neuronal differentiation markers. Radiation induced more apoptosis in NeuroD-positive cells than NeuroD-negative cells. We concluded that radiation activates JNK and induces apoptosis, especially in neural progenitor cells, resulting in the inhibition of neurogenesis. Our findings raise the possibility that JNK inhibition has therapeutic potential in protecting NSCs from the adverse effects of radiation.
机译：整个生命中，大量的神经干细胞（NSC）继续增殖并在中枢神经系统中生成神经元。电离辐射是神经胶质瘤患者的重要辅助治疗，可能会损害神经干细胞并引起神经元功能障碍，例如认知功能障碍和记忆力减退。然而，辐射作用对神经干细胞死亡和分化的确切机制仍然未知。在这里，我们发现辐射通过线粒体途径诱导了神经干细胞的凋亡，上调了Bax与Bcl-2的比例，并向细胞质释放了细胞色素c。辐射还将神经干细胞的神经元分化抑制了50％。在这三种应激相关的促丝裂原激活蛋白激酶（MAPK）中，只有c-Jun NH2末端激酶（JNK）在放射后的NSC中被激活。有趣的是，特异性抑制剂SP600125对JNK的抑制使NSC摆脱了凋亡并改善了神经元分化。此外，我们检查了辐射是否直接抑制神经元分化。辐射不影响NeuroD的启动子活性，NeuroD是调节神经元分化标志物表达的基本螺旋-环-螺旋转录因子。辐射在NeuroD阳性细胞中比NeuroD阴性细胞诱导更多的凋亡。我们得出的结论是，辐射激活JNK并诱导凋亡，尤其是在神经祖细胞中，从而导致神经发生抑制。我们的发现提高了JNK抑制作用在保护NSC免受放射不良影响方面具有治疗潜力的可能性。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号