The role of ATF6 in Cr(VI)-induced apoptosis in DF-1 cells

• Published in: Journal of hazardous materials 2021-05, Vol.410, p.124607-124607, Article 124607
• Main Authors: Zhang, Shuo, Zhao, Xiaona, Hao, Jiajia, Zhu, Yiran, Wang, Yue, Wang, Lumei, Guo, Shuhua, Yi, Hui, Liu, Yongxia, Liu, Jianzhu
• Format: Article
• Language: English
• Subjects: Apoptosis; ATF-6; ER stress; Hexavalent chromium; Mitochondria
• ISSN: 0304-3894; 1873-3336
• DOI: 10.1016/j.jhazmat.2020.124607

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. [Display omitted] •Cr(VI) induced apoptosis by Endoplasmic reticulum stress and mitochondrial damage.•ATF-6 regulated apoptosis by Endoplasmic reticulum stress and mitochondrial pathway.•ATF-6 siRNA reduced mitochondrial damage by inhibiting Endoplasmic reticulum stress.