在应对和高度应激时,ZBP1协调细胞死亡途径之间的动态过渡
Yinghao Fu1, Yifan Yang1, Qingqing Li1
1State Key Laboratory of Cellular Stress Biology, Cancer Research Center, School of Medicine, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, China.
The Journal of biological chemistry
|October 24, 2025
概括
在环境压力下,Z-DNA结合蛋白1 (ZBP1) 触发细胞死亡. 这项研究揭示了ZBP1介导的亡,亡和亡,独立于压力颗粒,为组织损伤提供了洞察力.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 毒理学 毒理学 毒理学
背景情况:
- Z-DNA结合蛋白1 (ZBP1) 是一个已知的Z型核酸传感器.
- 它在感染和发育中的作用已经确立,但它在环境应激反应中的功能在很大程度上是未知的.
研究的目的:
- 为了研究ZBP1介导的细胞死亡机制,在环境压力因素如和hyperosmotic条件下.
- 探索ZBP1,压力颗粒和细胞死亡途径之间的关系.
主要方法:
- 利用细胞死亡测试来监测ZBP1在和高度应激中的作用.
- 研究了使用抑制剂和基因切除的压力颗粒的参与.
- 进行全基因组的CRISPR/Cas9选,以确定关键的信号通路.
- 采用ZBP1淘汰赛 (KO) 鼠标来评估体内反应.
主要成果:
- 在压力中,ZBP1会在早期启动亡,然后过渡到亡和亡,特别是如果亡被抑制的话.
- 在这些环境压力下,压力颗粒的形成对于ZBP1介导的细胞死亡并不必不可少.
- 活性氧物种和KEAP1-NRF2通路是ZBP1-依赖细胞死亡的关键驱动因素.
- ZBP1 KO小鼠对诱导的细胞死亡和组织损伤表现出显著的抵抗力.
结论:
- 在应对环境压力因素时,ZBP1在调解细胞死亡方面发挥着重要作用.
- 环境压力诱导的亡可以独立于压力颗粒的形成.
- 研究结果强调ZBP1是细胞对毒素和环境挑战反应的关键参与者,这对理解组织损伤有意义.
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