...
首页> 外文期刊>Apoptosis >Chk1 has an essential role in the survival of differentiated cortical neurons in the absence of DNA damage
【24h】

Chk1 has an essential role in the survival of differentiated cortical neurons in the absence of DNA damage

机译:在没有DNA损伤的情况下,Chk1在分化皮质神经元的存活中起着至关重要的作用

获取原文
获取原文并翻译 | 示例
           

摘要

Neuronal death in the central nervous system contributes to the development of age-related neurodegeneration. The ATR/Chk1 pathway appears to function neuroprotectively to prevent DNA damage induced by cytotoxic agents. Here, we examine the function of Chk1 on cell viability of cortical neurons in the absence of additional DNA damaging stimuli. The Chk1-specific inhibitor, UCN-01, and the ATR inhibitor, Caffeine, cause neuronal apoptosis in differentiated neurons in the absence of additional treatment, whereas inhibition of ATM or Chk2, does not. UCN-01 treatment increased the detection of γ-H2AX phosphorylation, DNA strand breaks, and an activated p53-dependent DNA damage response (DDR), suggesting that Chk1 normally helps to maintain genomic stability. UCN-01 treatment also enhanced the apoptosis seen in neurons treated with DNA damaging agents, such as camptothecin (CPT). Our results indicate that Chk1 is essential for neuronal survival, and perturbation of this pathway increases a cell’s sensitivity to naturally accumulating DNA damage.
机译:中枢神经系统中的神经元死亡导致与年龄有关的神经变性的发展。 ATR / Chk1途径似乎具有神经保护功能,以防止细胞毒性剂诱导的DNA损伤。在这里,我们检查在没有其他DNA破坏性刺激的情况下,Chk1对皮质神经元细胞活力的功能。在没有其他治疗的情况下,Chk1特异性抑制剂UCN-01和ATR抑制剂咖啡因引起分化神经元的神经元凋亡,而抑制ATM或Chk2则没有。 UCN-01处理增加了对γ-H2AX磷酸化,DNA链断裂和激活的p53依赖性DNA损伤反应(DDR)的检测,表明Chk1通常有助于维持基因组稳定性。 UCN-01处理还增强了用DNA破坏剂(如喜树碱(CPT))处理的神经元中的凋亡。我们的结果表明,Chk1对于神经元的生存至关重要,并且对该途径的干扰会增加细胞对自然积累的DNA损伤的敏感性。

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