Silver nanoparticles activate endoplasmic reticulum stress signaling pathway in cell and mouse models: The role in toxicity evaluation

Lingling Huo, Rui Chen, Lin Zhao, Xiaofei Shi, Ru Bai, Dingxin Long, Feng Chen, Yuliang Zhao, Yan Zhong Chang, Chunying Chen

Research output: Contribution to journalArticle

81 Scopus citations

Abstract

Silver nanoparticles (AgNPs) attract considerable public attention both for their antimicrobial properties and their potential adverse effects. In the present study, endoplasmic reticulum (ER) stress was used as a sensitive and early biomarker to evaluate the toxic potential of AgNPs in three different human cell lines in vitro and in vivo in mice. In 16HBE cells, the activation of ER stress signaling pathway was observed by upregulated expression including xbp-1s, chop/. DDIT3, TRIB3, ADM2, BIP, Caspase-12, ASNS and HERP at either the mRNA and/or protein levels. However, these changes were not observed in HUVECs or HepG2 cells. Furthermore, mice experiments showed that different tissues had various sensitivities to AgNPs following intratracheal instillation exposure. The lung, liver and kidney showed significant ER stress responses, however, only the lung and kidney exhibited apoptosis by TUNEL assay. The artery and tracheal tissues had lower ER stress and apoptosis after exposure. The lowest observable effect concentrations (LOEC) were proposed based on evaluation of AgNP induced ER stress response in cell and mouse models. In summary, preliminary evaluation of AgNP toxicity by monitoring the ER stress signaling pathway provides new insights toward the understanding the biological impacts of AgNPs. The adverse effects of exposure to AgNPs may be avoided by rational use within the safe dose.

Original languageEnglish (US)
Pages (from-to)307-315
Number of pages9
JournalBiomaterials
Volume61
DOIs
StatePublished - Aug 1 2015

Keywords

  • Apoptosis
  • Cytotoxicity
  • Intratracheal instillation
  • Signaling pathway
  • Silver

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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