内质网
脂质过氧化
化学
活性氧
程序性细胞死亡
GPX4
诱导剂
脂滴
细胞生物学
细胞凋亡
生物化学
氧化应激
超氧化物歧化酶
生物
基因
谷胱甘肽过氧化物酶
作者
Zhiming Xing,Jiangyu Yan,Yun Miao,Yawen Ruan,Haojun Yao,Youkang Zhou,Yingqun Tang,Guorui Li,Zhibin Song,Yiyuan Peng,Jing Huang
标识
DOI:10.1021/acs.jmedchem.3c01652
摘要
Lethal lipid peroxidation caused by reactive oxygen species occurs in different types of programmed cell death, especially in ferroptosis. Ferroptosis inducers, which serve as small-molecule probes, can provide insight into the mechanism of ferroptosis and facilitate drug discovery. The classical ferroptosis inducers indirectly lead to lipid peroxidation; thus, it is difficult to explore lipid regulation during the ferroptotic process. In this study, we designed two quinazolinone-based lipophilic probes BODIQPy-TPA and QPy-TPA, which proved to directly induce lipid peroxidation by light irradiation in vitro. The probe BODIQPy-TPA, which was mainly distributed in the endoplasmic reticulum (ER), specifically triggered ferroptosis in B16 and HepG2 cells upon light irradiation. As a comparison, the probe QPy-TPA, which was mainly distributed in lipid droplets (LDs), induced cell death by a nonferroptotic pathway. Further lipidomic analysis revealed that these two probes caused different patterns of lipid regulation and lipid peroxidation, suggesting that ferroptosis might activate distinct lipid regulation.
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