China-Japan Friendship Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Department of Emergency, China-Japan Friendship Hospital, No. 2 Yinghua Dongjie, Beijing 100029, China.
Graduate School, Beijing University of Chinese Medicine, Beijing 100029, China.
Int Immunopharmacol. 2023 May;118:110083. doi: 10.1016/j.intimp.2023.110083. Epub 2023 Apr 5.
Sepsis is caused by complex infections, trauma, and major surgery that results in high morbidity and mortality. As one of the leading causes of death in the intensive care unit (ICU）, sepsis causes organ dysfunction and death via a vicious cycle of uncontrolled inflammatory responses and immunosuppression. Ferroptosis is an iron-dependent cellular death pathway driven by the accumulation of lipid peroxides, which occurs in sepsis. p53 is an important regulator of ferroptosis. Under intracellular/extracellular stimulation and pressure, p53 acts as a transcription factor to regulate the expression of downstream genes, which help cells/bodies to resist stimuli. p53 can also function independently as an important mediator. The understanding of key cellular and molecular mechanisms of ferroptosis facilitates the prognosis of sepsis. This article describes the molecular mechanism and role of p53 in sepsis-induced ferroptosis, and introduces some potential therapeutic targets for sepsis-induced ferroptosis, which highlights the dominant and potential therapeutic role of p53 in sepsis. Keywords: p53, acetylation, Sirt3, ferroptosis, sepsis, therapy.
脓毒症是由复杂的感染、创伤和大手术引起的，导致高发病率和死亡率。作为重症监护病房（ICU）中主要的死亡原因之一，脓毒症通过失控的炎症反应和免疫抑制的恶性循环导致器官功能障碍和死亡。铁死亡是一种由脂质过氧化物积累驱动的铁依赖性细胞死亡途径，发生在脓毒症中。p53 是铁死亡的重要调节因子。在细胞内/细胞外刺激和压力下，p53 作为转录因子发挥作用，调节下游基因的表达，帮助细胞/机体抵抗刺激。p53 也可以独立作为重要的介质发挥作用。了解铁死亡的关键细胞和分子机制有助于脓毒症的预后。本文描述了 p53 在脓毒症诱导的铁死亡中的分子机制和作用，并介绍了一些脓毒症诱导的铁死亡的潜在治疗靶点，这突出了 p53 在脓毒症中的主导和潜在的治疗作用。关键词：p53、乙酰化、Sirt3、铁死亡、脓毒症、治疗。
