title: Silver nanoparticles activate endoplasmic reticulum stress signaling pathway in cell and mouse models: The role in toxicity evaluation.
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.
authors.affiliation: Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, Key Laboratory of Molecular and Cellular Biology of Ministry of Education, College of Life Science, Hebei Normal University, Shijiazhuang 050016, PR China; CAS Key Lab for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience & Technology of China, Beijing 100190, PR China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Huo
authors.affiliation: CAS Key Lab for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience & Technology of China, Beijing 100190, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.affiliation: CAS Key Lab for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience & Technology of China, Beijing 100190, PR China; School of Public Health, University of South China, Hengyang 421001, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhao
authors.affiliation: CAS Key Lab for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience & Technology of China, Beijing 100190, PR China; School of Public Health, University of South China, Hengyang 421001, PR China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Shi
authors.affiliation: CAS Key Lab for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience & Technology of China, Beijing 100190, PR China.
authors.forename: Ru
authors.initials: R
authors.lastname: Bai
authors.affiliation: School of Public Health, University of South China, Hengyang 421001, PR China.
authors.forename: Dingxin
authors.initials: D
authors.lastname: Long
authors.affiliation: School of Public Health, University of South China, Hengyang 421001, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.affiliation: CAS Key Lab for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience & Technology of China, Beijing 100190, PR China.
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, Key Laboratory of Molecular and Cellular Biology of Ministry of Education, College of Life Science, Hebei Normal University, Shijiazhuang 050016, PR China. Electronic address: chang7676@163.com.
authors.forename: Yan-Zhong
authors.initials: YZ
authors.lastname: Chang
authors.affiliation: CAS Key Lab for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience & Technology of China, Beijing 100190, PR China. Electronic address: chenchy@nanoctr.cn.
authors.forename: Chunying
authors.initials: C
authors.lastname: Chen
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D008297:Male; D008422:Materials Testing; D053768:Metal Nanoparticles / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D012834:Silver / Q000633:toxicity*
chemical_list: D017382:Reactive Oxygen Species; D012834:Silver
keywords: Apoptosis; Cytotoxicity; Intratracheal instillation; Signaling pathway; Silver