铁抑制素-1抑制丙酮醛诱导的小鼠肺泡巨噬细胞铁死亡  

FER-1 inhibits methylglyoxal-induced ferroptosis in mouse alveolar macrophages in vitro

作　　者：张琪 计泽朝 加沙尔·阿拜 王友达 阿不都许库尔·阿不力米提[1] ZHANG Qi;JI Zezhao;JIASHAER·Abai;WANG Youda;ABUDUXUKUER·Abulimiti(Department of Histology and Embryology,School of Basic Medical Sciences,Xinjiang Medical University,Urumqi 830000,China)

机构地区：[1]新疆医科大学基础医学院组织与胚胎学教研室,新疆维吾尔自治区乌鲁木齐830000

出　　处：《南方医科大学学报》2024年第12期2443-2448,共6页Journal of Southern Medical University

基　　金：国家自然科学基金(32060158)。

摘　　要：目的探讨丙酮醛(MG)对小鼠肺泡巨噬细胞的损伤及铁死亡抑制剂铁抑制素-1(FER-1)在其中的作用机制。方法采用小鼠肺泡巨噬细胞来源的MH-S细胞体外培养,分别用MG及FER-1进行处理,建立细胞损伤及损伤挽救模型。分别设置对照组:MH-S正常培养、MG组:90μg/mL MG、MG+FER-1组:90μg/mL MG+10μmol/mL FER-1、FER-1组:10μmol/mL FER-1。用双氯荧光素(DCFH-DA)检测细胞内ROS水平,脂质氧化(MDA)试剂盒检测MDA含量,细胞亚铁比色法检测亚铁离子(Fe^(2+))含量;线粒体膜电位检测试剂盒(JC-1)检测线粒体膜电位变化,Western blotting检测谷胱甘肽过氧化物酶4(GPX4)、长链酰基辅酶A合酶4(ACSL4)的表达水平。结果90μg/mL MG处理MH-S细胞24 h,GPX4的表达水平降低(P<0.001),ACSL4的表达水平升高(P<0.01),同时出现细胞内亚铁离子浓度升高,线粒体膜电位丢失,胞内活性氧水平升高,丙二醛含量增多等现象,最终导致细胞存活率降低(P<0.01)。通过FER-1共同干预后,GPX4的表达升高、ACSL4的表达降低,胞内铁离子浓度降低、线粒体膜电位恢复、活性氧水平降低,丙二醛含量减少(P<0.001)。结论MG能够剂量依赖性诱导MH-S细胞发生铁死亡,而铁死亡抑制剂FER-1能够挽救MG所导致的铁死亡。Objective To investigate the inhibitory effect of FER-1 on methylglyoxal-induced ferroptosis in cultured mouse alveolar macrophages.Methods MH-S cells derived from mouse alveolar macrophages treated with 90μg/mL methylglyoxal,10μmol/mL FER-1MG+FER-1,or both were examined for intracellular reactive oxygen species(ROS),malondialdehyde(MDA)and ferrous ion(Fe^(2+))levels and changes in mitochondrial membrane potential.Western blotting was performed to detect the protein expression levels of glutathione peroxidase 4(GPX4)and long-chain acyl-CoA synthase 4(ACSL4).Results Methylglyoxal treatment of MH-S cells for 24 h significantly decreased the protein expression level of GPX4,upregulated the protein expression of ACSL4,increased intracellular concentrations of ferrous ions,ROS and MDA,caused loss of mitochondrial membrane potential,and decreased cell viability.Treatment of the cells with FER-1 effectively attenuated these detrimental effects of methylglyoxal in MH-S cells by increasing GPX4 expression,reducing ACSL4 expression and intracellular ferrous ions,ROS and MDA levels,and restoring the mitochondrial membrane potential.Conclusion Methylglyoxal can induce ferroptosis in MH-S cells in a dose-dependent manner,and FER-1 can rescue the cells from methylglyoxal-induced ferroptosis.

关 键 词：铁抑制素-1 小鼠肺泡巨噬细胞 丙酮醛 铁死亡 

分 类 号：R587.2[医药卫生—内分泌] R563[医药卫生—内科学]