研究人员发现Z-DNA结合蛋白 1 (ZBP1)，一种 Z-核酸受体，通过触发受体相互作用蛋白激酶 3 (RIPK3) 依赖性细胞死亡来介导中暑。 热应激通过热休克转录因子 1 (HSF1) 增加ZBP1的表达，并通过独立于核酸传感作用的机制激活ZBP1。ZBP1、RIPK3或混合谱系激酶域样 (MLKL) 和caspase-8的缺失降低了热应激诱导的循环衰竭、器官损伤和致死率。 因此，ZBP1似乎具有协调宿主对热应激反应的第二个功能。
据介绍，中暑是一种由热应激引起的危及生命的疾病，与循环衰竭和多器官功能障碍有关。 如果全球变暖持续下去，中暑可能会成为世界范围内更突出的死亡原因，但其致病机制尚不清楚。
附：英文原文
Title: Z-DNA binding protein 1 promotes heatstroke-induced cell death
Author: Fangfang Yuan, Jizhen Cai, Jianfeng Wu, Yiting Tang, Kai Zhao, Fang Liang, Fanglin Li, Xinyu Yang, Zhihui He, Timothy R. Billiar, Haichao Wang, Lei Su, Ben Lu
Issue&Volume: 2022-05-06
Abstract: Heatstroke is a heat stress–induced, life-threatening condition associated with circulatory failure and multiple organ dysfunctions. If global warming continues, heatstroke might become a more prominent cause of mortality worldwide, but its pathogenic mechanism is not well understood. We found that Z-DNA binding protein 1 (ZBP1), a Z–nucleic acid receptor, mediated heatstroke by triggering receptor-interacting protein kinase 3 (RIPK3)–dependent cell death. Heat stress increased the expression of ZBP1 through heat shock transcription factor 1 (HSF1) and activated ZBP1 through a mechanism independent of the nucleic acid sensing action. Deletion of ZBP1, RIPK3, or both mixed lineage kinase domain-like (MLKL) and caspase-8 decreased heat stress–induced circulatory failure, organ injury, and lethality. Thus, ZBP1 appears to have a second function that orchestrates host responses to heat stress.
DOI: abg5251
Source: https://www.science.org/doi/10.1126/science.abg5251