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首页> 外文期刊>Archives of Toxicology >The role of unfolded protein response and ER-phagy in quantum dots-induced nephrotoxicity: an in vitro and in vivo study
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The role of unfolded protein response and ER-phagy in quantum dots-induced nephrotoxicity: an in vitro and in vivo study

机译:展开蛋白质反应和ER-Phagy在量子点诱导的肾毒性中的作用:体外和体内研究

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摘要

Unfolded protein response (UPR) and endoplasmic reticulum (ER)-phagy are essential for cell homeostasis. Quantum dots (QDs), which have been widely used for biomedical applications, can accumulate in the kidney tissues and may cause renal dysfunction. However, the molecular mechanism of QDs-induced nephrotoxicity is still obscure. The present study was aimed to elucidate the role and mechanism of UPR and ER-phagy in QDs-induced nephrotoxicity. Herein, human embyronic kidney (HEK) cells were exposed to 15, 30, 45, and 60 nM cadmium telluride (CdTe)-QDs for 12 and 24 h. And CdTe-QDs (30-60 nM) inhibited the HEK cell viability. The clathrin-dependent endocytosis was determined as the main pathway of CdTe-QDs cellular uptake. Within cells, CdTe-QDs disrupted ER ultrastructure and induced UPR and FAM134B-dependent ER-phagy. Blocking UPR with inhibitors or siRNA rescued the FAM134B-dependent ER-phagy, which was triggered by CdTe-QDs. Moreover, suppression of UPR or FAM134B-dependent ER-phagy restored the cell vability. In vivo, mice were intravenously injected with 8 and 16 nmol/kg body weight CdTe-QDs for 24 h. Kidney was shown as one of highest distributed organs of CdTe-QDs, resulting in renal dysfunction, as well as UPR and FAM134B-dependent ER-phagy in it. Thus, for the first time, we demonstrated that ER-phagy can be triggered by nanomaterials both in vitro and in vivo. In addition, blocking of UPR and ER-phagy showed protective effects against CdTe-QDs-induced toxicity in kideny cells. Notably, a secreted alkaline phosphatase reporter gene system has been developed as a sensitive and rapid method for evaluating the ER quality under the exposure of nanomaterials.
机译:展开的蛋白质反应(UPR)和内质网(ER) - 对照对细胞稳态至关重要。已广泛用于生物医学应用的量子点(QDS)可以积聚在肾组织中,并可能导致肾功能不全。然而,QDS诱导的肾毒性的分子机制仍然模糊不清。本研究旨在阐明QDS诱导的肾毒性UPR和ER-Phagy的作用和机制。在此,人呼吸肾(HEK)细胞暴露于15,30,45和60nM碲化镉(CdTe)-Qds 12和24小时。和CDTE-QD(30-60nm)抑制了HEK细胞活力。克拉林依赖性内吞作用被确定为CDTE-QDS细胞摄取的主要途径。在细胞内,CDTE-QDS中断ER超微结构并诱导UPR和FAM134B依赖性的ER-Phagy。阻断UPR与抑制剂或siRNA救出了由CDTE-QD触发的FAM134B依赖的ER-Phagy。此外,抑制UPR或FAM134B依赖性的ER-Phagy恢复了细胞不变。在体内,用8和16 nmol / kg体重CdTe-Qds静脉内注射小鼠24小时。肾脏被显示为CdTe-QD的最高分布器官之一,导致肾功能障碍,以及其中的upr和Fam134b依赖的er-phagy。因此,首次证明ER-Phagy可以通过体外和体内纳米材料触发。此外,UPR和ER-Phagy的阻断表现出对肾细胞中CDTE-QDS诱导的毒性的保护作用。值得注意的是,分泌的碱性磷酸酶报告基因系统已成为一种敏感和快速的方法,用于评估纳米材料暴露下的ER质量。

著录项

  • 来源
    《Archives of Toxicology》 |2018年第4期|共14页
  • 作者单位

    Xiamen Univ Sch Publ Hlth State Key Lab Mol Vaccinol &

    Mol Diagnost Xiamen 361102 Peoples R;

    Xiamen Univ Sch Publ Hlth State Key Lab Mol Vaccinol &

    Mol Diagnost Xiamen 361102 Peoples R;

    Xiamen Univ Sch Publ Hlth State Key Lab Mol Vaccinol &

    Mol Diagnost Xiamen 361102 Peoples R;

    Xiamen Univ Sch Publ Hlth State Key Lab Mol Vaccinol &

    Mol Diagnost Xiamen 361102 Peoples R;

    Xiamen Univ Sch Publ Hlth State Key Lab Mol Vaccinol &

    Mol Diagnost Xiamen 361102 Peoples R;

    Xiamen Univ Sch Publ Hlth State Key Lab Mol Vaccinol &

    Mol Diagnost Xiamen 361102 Peoples R;

    Xiamen Univ Sch Publ Hlth State Key Lab Mol Vaccinol &

    Mol Diagnost Xiamen 361102 Peoples R;

    Xiamen Univ Res Inst Biomimet &

    Soft Matter Xiamen 361005 Peoples R China;

    Xiamen Univ Res Inst Biomimet &

    Soft Matter Xiamen 361005 Peoples R China;

    Xiamen Univ Res Inst Biomimet &

    Soft Matter Xiamen 361005 Peoples R China;

    Xiamen Univ Sch Publ Hlth State Key Lab Mol Vaccinol &

    Mol Diagnost Xiamen 361102 Peoples R;

    Xiamen Univ Sch Publ Hlth State Key Lab Mol Vaccinol &

    Mol Diagnost Xiamen 361102 Peoples R;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 毒物学(毒理学);
  • 关键词

    Quantum dots; Unfolded protein response; ER-phagy; Endoplasmic reticulum quality control; Autophagy; FAM134B; Kidney;

    机译:量子点;展开的蛋白质反应;ER-PHAGY;内质网状质量控制;自噬;FAM134B;肾;

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