Xu Yifei, Qu Xintian, Liang Minghao, Huang Di, Jin Minyan, Sun Lili, Chen Xianhai, Liu Fen, Qiu Zhanjun
First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China.
College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.
Front Med (Lausanne). 2024 Sep 17;11:1457882. doi: 10.3389/fmed.2024.1457882. eCollection 2024.
By engaging in redox processes, ferroptosis plays a crucial role in sepsis-induced acute lung injury (ALI). Although iron stimulates calcium signaling through the stimulation of redox-sensitive calcium pathways, the function of calcium signals in the physiological process of ferroptosis in septic ALI remains unidentified. Iron homeostasis disequilibrium in ferroptosis is frequently accompanied by aberrant calcium signaling. Intracellular calcium overflow can be a symptom of dysregulation of the cellular redox state, which is characterized by iron overload during the early phase of ferroptosis. This can lead to disruptions in calcium homeostasis and calcium signaling. The mechanisms controlling iron homeostasis and ferroptosis are reviewed here, along with their significance in sepsis-induced acute lung injury, and the potential role of calcium signaling in these processes is clarified. We propose that the development of septic acute lung injury is a combined process involving the bidirectional interaction between iron homeostasis and calcium signaling. Our goal is to raise awareness about the pathophysiology of sepsis-induced acute lung injury and investigate the relationship between these mechanisms and ferroptosis. We also aimed to develop calcium-antagonistic therapies that target ferroptosis in septic ALI and improve the quality of survival for patients suffering from acute lung injury.
通过参与氧化还原过程，铁死亡在脓毒症诱导的急性肺损伤（ALI）中起着关键作用。尽管铁通过刺激氧化还原敏感的钙途径来刺激钙信号传导，但钙信号在脓毒症ALI中铁死亡生理过程中的作用仍不明确。铁死亡中的铁稳态失衡常伴有异常的钙信号传导。细胞内钙溢出可能是细胞氧化还原状态失调的一种表现，其特征是在铁死亡早期出现铁过载。这可能导致钙稳态和钙信号传导的破坏。本文综述了控制铁稳态和铁死亡的机制及其在脓毒症诱导的急性肺损伤中的意义，并阐明了钙信号传导在这些过程中的潜在作用。我们提出，脓毒症急性肺损伤的发展是一个涉及铁稳态和钙信号传导双向相互作用的联合过程。我们的目标是提高对脓毒症诱导的急性肺损伤病理生理学的认识，并研究这些机制与铁死亡之间的关系。我们还旨在开发针对脓毒症ALI中铁死亡的钙拮抗疗法，提高急性肺损伤患者的生存质量。
