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

机译:ATF6在Cr(Ⅵ)中的作用 - 诱导DF-1细胞的细胞凋亡

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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 downregulated 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.
机译:六价铬(Cr(VI))是环境中常见的重金属污染物,并已被证明具有细胞毒性。在这项研究中,我们旨在探讨激活转录因子6(ATF-6)在Cr(VI)诱导的鸡胚胚胎细胞系(DF-1)凋亡中的作用。首先,将DF-1细胞暴露于Cr(VI)以建立细胞毒性模型,然后分析细胞凋亡和ATF-6蛋白质水平。通过沉默ATF-6基因,检查凋亡率和凋亡蛋白的变化。为了进一步探索ATF-6,内质网(ER)应激,线粒体功能,反应性氧物质(ROS)水平以及相关途径的调节机制。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)还原和ER应力。同时,ATF-6沉默降低了凋亡率和ER应力水平,显示XBP-1,Perk,GRP78,Caspase-12,切割的Caspase-3和Bcl-2的增加。进一步的分析发现,ATF-6沉默下调的ROS并导致MMP损失,表明ATF-6沉默抑制CR(VI)诱导的线粒体损伤。总之,该研究表明,ATF-6在Cr(VI)中发挥着重要的调节作用,诱导了通过ER应激和线粒体途径的DF-1细胞凋亡。

著录项

  • 来源
    《Journal of Hazardous Materials》 |2021年第15期|124607.1-124607.14|共14页
  • 作者单位

    Shandong Agr Univ Coll Vet Med Tai An 271018 Shandong Peoples R China;

    Shandong Agr Univ Res Ctr Anim Dis Control Engn Tai An 271018 Shandong Peoples R China;

    Shandong Agr Univ Coll Vet Med Tai An 271018 Shandong Peoples R China;

    Shandong Agr Univ Coll Vet Med Tai An 271018 Shandong Peoples R China;

    Shandong Agr Univ Coll Vet Med Tai An 271018 Shandong Peoples R China;

    Shandong Agr Univ Coll Vet Med Tai An 271018 Shandong Peoples R China;

    Shandong Agr Univ Coll Vet Med Tai An 271018 Shandong Peoples R China;

    Anim Husb & Vet Serv Ctr Taian City Tai An 271000 Shandong Peoples R China;

    Shandong Agr Univ Res Ctr Anim Dis Control Engn Tai An 271018 Shandong Peoples R China;

    Shandong Agr Univ Coll Vet Med Tai An 271018 Shandong Peoples R China;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    Hexavalent chromium; ATF-6; Apoptosis; ER stress; Mitochondria;

    机译:六价铬;ATF-6;凋亡;ER应激;线粒体;

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