Hao Meng-Yuan, Li Hong-Jie, Han Hang-Shen, Chu Ti, Wang Yan-Wen, Si Wei-Rong, Jiang Qi-Ying, Wu Dong-Dong
Henan International Joint Laboratory for Nuclear Protein Regulation, School of Basic Medical Sciences, School of Stomatology, Henan University, Kaifeng, Henan, 475004, China.
School of Basic Medical Sciences, Henan University, Kaifeng, Henan, 475004, China.
Apoptosis. 2025 Apr;30(3-4):616-635. doi: 10.1007/s10495-024-02057-x. Epub 2025 Jan 20.
Necroptosis is a finely regulated programmed cell death process involving complex molecular mechanisms and signal transduction networks. Among them, receptor-interacting protein kinase 1 (RIPK1), receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like protein are the key molecules regulating this process. In recent years, gasotransmitters such as nitric oxide, carbon monoxide and hydrogen sulfide have been suggested to play a regulatory role in necroptosis. This paper reviews the evidence that these gasotransmitters are involved in the regulation of necroptosis by influencing the production of reactive oxygen species, regulating the modification of S subunits of RIPK1 and RIPK3, regulating inflammatory mediators, and signal transduction. In addition, this review explores the potential therapeutic applications of these gasotransmitters in pathological conditions such as cardiovascular disease and ischemia-reperfusion injury. Although some studies have revealed the important role of gasotransmitters in necroptosis, the specific mechanism of action is still not fully understood. Future research is needed to further elucidate the molecular mechanisms of gasotransmitters in precisely regulating necroptosis, which will help develop new therapeutic strategies to prevent and treat related diseases.
坏死性凋亡是一个精细调控的程序性细胞死亡过程，涉及复杂的分子机制和信号转导网络。其中，受体相互作用蛋白激酶1（RIPK1）、受体相互作用蛋白激酶3（RIPK3）和混合谱系激酶结构域样蛋白是调节这一过程的关键分子。近年来，一氧化氮、一氧化碳和硫化氢等气体信号分子被认为在坏死性凋亡中发挥调节作用。本文综述了这些气体信号分子通过影响活性氧的产生、调节RIPK1和RIPK3的S亚基修饰、调节炎症介质以及信号转导等方式参与坏死性凋亡调控的证据。此外，本综述还探讨了这些气体信号分子在心血管疾病和缺血再灌注损伤等病理状况下的潜在治疗应用。尽管一些研究已经揭示了气体信号分子在坏死性凋亡中的重要作用，但其具体作用机制仍未完全阐明。未来需要进一步研究以深入阐明气体信号分子精确调控坏死性凋亡的分子机制，这将有助于开发预防和治疗相关疾病的新策略。
