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

Abstract

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.

Keywords: ATF-6; Apoptosis; ER stress; Hexavalent chromium; Mitochondria.