小胶质细胞
细胞生物学
细胞凋亡
组织蛋白酶B
组织蛋白酶D
神经炎症
活性氧
膜联蛋白
组织蛋白酶
生物
程序性细胞死亡
线粒体
化学
生物化学
免疫学
炎症
酶
作者
Zheyu Zhang,Ruozheng Pi,Yuheng Jiang,Mashaal Ahmad,Heng Luo,Jieya Luo,Jie Yang,Baofei Sun
标识
DOI:10.1177/09603271231172724
摘要
Arsenic is a prevalent environmental pollutant that targets the nervous system of living beings. Recent studies indicated that microglial injury could contribute to neuroinflammation and is associated with neuronal damage. Nevertheless, the neurotoxic mechanism underlying the arsenic-induced microglial injury requires additional research. This study explores whether cathepsin B promotes microglia cell damage caused by NaAsO2. Through CCK-8 assay and Annexin V-FITC and PI staining, we discovered that NaAsO2 induced apoptosis in BV2 cells (a microglia cell line). NaAsO2 was verified to increase mitochondrial membrane permeabilization (MMP) and promote the generation of reactive oxygen species (ROS) through JC-1 staining and DCFDA assay, respectively. Mechanically, NaAsO2 was indicated to increase the expression of cathepsin B, which could stimulate pro-apoptotic molecule Bid into the activated form, tBid, and increase lysosomal membrane permeabilization by Immunofluorescence and Western blot assessment. Subsequently, apoptotic signaling downstream of increased mitochondrial membrane permeabilization was activated, promoting caspase activation and microglial apoptosis. Cathepsin B inhibitor CA074-Me could mitigate the damage of microglial. In general, we found that NaAsO2 induced microglia apoptosis and depended on the role of the cathepsin B-mediated lysosomal-mitochondrial apoptosis pathway. Our findings provided new insight into NaAsO2-induced neurological damage.
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