细胞凋亡
基因沉默
ATF6
活性氧
细胞生物学
化学
未折叠蛋白反应
内质网
氧化应激
线粒体
分子生物学
生物
生物化学
基因
作者
Shuo Zhang,Xiaona Zhao,Jiajia Hao,Yiran Zhu,Yue Wang,Lumei Wang,Shuai Guo,Hongming Yi,Yongxia Liu,Jianzhu Liu
标识
DOI:10.1016/j.jhazmat.2020.124607
摘要
Hexavalent chromium (Cr(VI)) is a common heavy metal pollutant in environment and has been proved possessing the cytotoxicity. In this study, we aimed to investigate the role of activating transcription factor 6 (ATF-6) in apoptosis of chicken embryo fibroblasts cell line (DF-1) induced by Cr(VI). Firstly, DF-1 cells were exposed to Cr(VI) to establish the cytotoxicity model, then the cell apoptosis and ATF-6 protein level were analyzed. By silencing ATF-6 gene, changes of the apoptosis rate and apoptotic proteins were examined. To further explore the regulatory mechanism of ATF-6, endoplasmic reticulum (ER) stress, mitochondrial function, reactive oxygen species (ROS) level, as well as the related pathway were evaluated. Results showed that Cr(VI) can result in DF-1 cell apoptosis, along with mitochondrial membrane potential (MMP) reducing and ER stress. Meanwhile, ATF-6 silencing lowered the apoptosis rate and ER stress level, showing with the decrease of XBP-1, PERK, GRP78, Caspase-12, Cleaved Caspase-3 and the increase of Bcl-2. Further analysis found that ATF-6 silencing down-regulated ROS and caused MMP loss, suggesting that ATF-6 silencing inhibited Cr(VI)-induced mitochondrial damage. In conclusion, this study indicate that ATF-6 plays an important regulatory role in Cr(VI)-induced DF-1 cell apoptosis through the ER stress and mitochondrial pathway.
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