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.

六价铬（Cr（VI））是环境中常见的重金属污染物，已被证明具有细胞毒性。在这项研究中，我们旨在研究激活转录因子6（ATF-6）在六价铬（Cr）诱导的鸡胚成纤维细胞系（DF-1）凋亡中的作用。首先，将DF-1细胞暴露于Cr（VI）建立细胞毒性模型，然后分析细胞凋亡和ATF-6蛋白水平。通过使ATF-6静音检测基因，凋亡率和凋亡蛋白的变化。为了进一步探讨ATF-6的调节机制，评估了内质网（ER）应激，线粒体功能，活性氧（ROS）水平以及相关途径。结果表明，Cr（VI）可以导致DF-1细胞凋亡，以及线粒体膜电位（MMP）降低和内质网应激。同时，ATF-6沉默降低了细胞凋亡率和ER应激水平，表现为XBP-1，PERK，GRP78，Caspase-12，Cleaved Caspase-3的减少和Bcl-2的增加。进一步分析发现，ATF-6沉默下调了ROS并导致MMP丢失，这表明ATF-6沉默抑制Cr（VI）诱导的线粒体损伤。总之，这项研究表明，ATF-6通过内质网应激和线粒体途径在Cr（VI）诱导的DF-1细胞凋亡中起着重要的调节作用。