...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochemistry >Conversion of Death Signal into Survival Signal by Redox Signaling
【24h】

Conversion of Death Signal into Survival Signal by Redox Signaling

机译：通过氧化还原信号将死亡信号转换为生存信号

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Reperfusion of ischemic myocardium produces reactive oxygen species (ROS) and results in apoptotic cell death and DNA fragmentation. Several redox-sensitive anti- and pro-apoptotic transcription factors including nuclear factor kappaB (NF-kappaB) and heterodimeric transcription factor AP-1 progressively and steadily increase in the heart as a function of the duration of ischemia and reperfusion. When the heart is adapted to ischemic stress by repeated short-term ischemia and reperfusion, NF-kappaB remains high, while AP-1 is lowered to almost baseline value. The anti-apoptotic gene Bcl-2 is down-regulated in the ischemic/reperfused heart, while it is upregulated in the adapted myocardium. Cardioprotective abilities of the adapted myocardium are abolished when heart is pre-perfused with N-acetyl cysteine to scavenge ROS, suggesting a role of redox signaling. Mammalian heart is protected by several defense systems, which include, among others, the redox-regu-lated protein thioredoxin. Reperfusion of ischemic myocardium results in the downregulation of thioredoxin 1 (Trx 1) expression, which was upregulated in the adapted myocardium. The increased expression of Trx 1 is completely blocked with an inhibitor of Trx 1, cis-diammine-dichloroplatinum, which also abolished cardioprotection afforded by ischemic adaptation. The cardioprotective role of Trx 1 is further confirmed with transgenic mouse hearts overexpressing Trx 1. The Trx 1 mouse hearts displayed significantly improved post-ischemic ventricular recovery and reduced myocardial infarct size and apoptosis compared to the corresponding wild-type mouse hearts. The results of this study implicate a crucial role of redox signaling in transmitting anti-death signal.
机译：缺血性心肌的再灌注产生活性氧（ROS），并导致凋亡性细胞死亡和DNA片段化。心脏中几种氧化还原敏感的抗凋亡和促凋亡转录因子，包括核因子κB（NF-kappaB）和异二聚体转录因子AP-1，随着缺血和再灌注持续时间的增加而逐渐稳定地增加。当通过反复的短期缺血和再灌注使心脏适应缺血应激时，NF-κB保持较高水平，而AP-1降低至几乎基线值。抗凋亡基因Bcl-2在缺血/再灌注心脏中被下调，而在适应的心肌中被上调。当心脏预先用N-乙酰基半胱氨酸灌注以清除ROS时，适应的心肌的心脏保护能力就会消失，这表明氧化还原信号的作用。哺乳动物的心脏受到多种防御系统的保护，其中包括氧化还原调节蛋白硫氧还蛋白。缺血心肌的再灌注导致硫氧还蛋白1（Trx 1）表达的下调，而后者在适应的心肌中被上调。 Trx 1的表达增加被Trx 1的抑制剂完全阻断，即顺式二氨基二氯铂，也消除了缺血适应性的心脏保护作用。用过表达Trx 1的转基因小鼠心脏进一步证实了Trx 1的心脏保护作用。与相应的野生型小鼠心脏相比，Trx 1小鼠心脏显示出明显改善的缺血后心室恢复，并减少了心肌梗塞的大小和细胞凋亡。这项研究的结果暗示了氧化还原信号在传输抗死亡信号中的关键作用。

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