Department of Anatomy, Biochemistry & Physiology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96813, USA.
Department of Microbiology and Immunology, School of Medicine, Keio University, Tokyo 160-8582, Japan.
Cells. 2022 Apr 20;11(9):1399. doi: 10.3390/cells11091399.
Ferroptosis is an iron-dependent form of regulated cell death and is distinct from other conventional forms of regulated cell death. It is often characterized by the dysfunction of the antioxidant selenoprotein glutathione peroxidase 4 (GPX4) antioxidant system. This loss of antioxidant capacity leads to the peroxidation of lipids and subsequent compromised plasma membrane structure. Disruption of the GPX4 antioxidant system has been associated with various conditions such as cardiomyopathy and ischemia-reperfusion (I/R) injury. GPX4 regulates lipid peroxidation, and chemical or genetic inhibition of GPX4 leads to reduced cardiac function. Iron chelators or antioxidants can be used for inhibiting ferroptosis, which restores functionality in in vivo and ex vivo experiments and confers overall cardioprotective effects against I/R injury. Moreover, suppression of ferroptosis also suppresses inflammation and limits the extent of left ventricle remodeling after I/R injury. Future research is necessary to understand the role of ferroptosis following an ischemic incident and can lead to the discovery of more potential therapeutics that prevent ferroptosis in the heart.
铁死亡是一种依赖铁的调节性细胞死亡形式，与其他传统的调节性细胞死亡形式不同。它通常的特征是抗氧化硒蛋白谷胱甘肽过氧化物酶 4 (GPX4) 抗氧化系统的功能障碍。这种抗氧化能力的丧失导致脂质过氧化，随后破坏质膜结构。GPX4 抗氧化系统的破坏与心肌病和缺血再灌注 (I/R) 损伤等各种情况有关。GPX4 调节脂质过氧化，化学或遗传抑制 GPX4 会导致心脏功能降低。铁螯合剂或抗氧化剂可用于抑制铁死亡，这在体内和体外实验中恢复了功能，并对 I/R 损伤产生整体的心脏保护作用。此外，抑制铁死亡还可以抑制炎症，限制 I/R 损伤后左心室重构的程度。有必要进行未来的研究以了解缺血事件后铁死亡的作用，并可能发现更多预防心脏中铁死亡的潜在治疗方法。
