百草枯
下调和上调
GPX4
氧化应激
程序性细胞死亡
A549电池
脂质过氧化
细胞生物学
化学
活性氧
细胞外
细胞凋亡
药理学
癌症研究
生物
生物化学
基因
过氧化氢酶
谷胱甘肽过氧化物酶
作者
Qiqi Cai,Qingya Shen,Weimin Zhu,Sheng Zhang,Jingjing Ke,Zhongqiu Lu
标识
DOI:10.1016/j.tiv.2023.105655
摘要
Paraquat (PQ) is an environmentally friendly and efficient herbicide, but PQ misuse or intentional self-use can cause death through multiple organ damage and can cause acute lung injury. Existing clinical treatments alleviate symptoms but do not significantly improve the mortality rate. Ferroptosis is a type of necrosis that presents in a manner very similar to the cell damage induced by high doses of PQ, but the role of ferroptosis in paraquat-induced lung injury remains unclear. In this study, we aimed to explore the role of ferroptosis in PQ-induced A549 cell injury and identify the potential mechanisms and critical sites of protection against PQ-induced A549 injury by ferroptosis inhibitors. We found that the ferroptosis inhibitors Ferr-1 and Lip-1 inhibit ferroptosis by attenuating oxidative stress through the upregulation of NRF2 gene expression. The protective role of the ferroptosis inhibitor Dfo was most evident in paraquat-induced cell injury. Dfo inhibited ferroptosis by iron chelation and promoted NRF2 protein level reduction. NRF2 attenuated PQ-induced ferroptosis in A549 cells, mainly through the upregulation of SLC40A1 to encourage the movement of iron to the extracellular side to alleviate iron overload, and the upregulation of SLC7A11 to promote the expression of GPX4 to inhibit lipid peroxidation.
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