Zinc Oxide Nanoparticles Induce Autophagy and Apoptosis via Oxidative Injury and Pro-Inflammatory Cytokines in Primary Astrocyte Cultures
The present study examined the potential toxic concentrations of zinc oxide nanoparticles (ZnO NPs) and associated autophagy and apoptosis-related injuries in primary neocortical astrocyte cultures. Concentrations of ZnO NPs ≥3 μg/mL induced significant toxicity in the astrocytes....
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doaj-383d8e0313de4e64bf2b9d29cca02d812020-11-25T00:22:51ZengMDPI AGNanomaterials2079-49912019-07-0197104310.3390/nano9071043nano9071043Zinc Oxide Nanoparticles Induce Autophagy and Apoptosis via Oxidative Injury and Pro-Inflammatory Cytokines in Primary Astrocyte CulturesWoo-Ju Song0Myung-Seon Jeong1Dong-Min Choi2Kil-Nam Kim3Myung-Bok Wie4Department of Veterinary Toxicology, College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, Chuncheon 24341, KoreaChuncheon Center, Korean Basic Science Institute, Chuncheon 24341, KoreaDepartment of Veterinary Toxicology, College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, Chuncheon 24341, KoreaChuncheon Center, Korean Basic Science Institute, Chuncheon 24341, KoreaDepartment of Veterinary Toxicology, College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, Chuncheon 24341, KoreaThe present study examined the potential toxic concentrations of zinc oxide nanoparticles (ZnO NPs) and associated autophagy and apoptosis-related injuries in primary neocortical astrocyte cultures. Concentrations of ZnO NPs ≥3 μg/mL induced significant toxicity in the astrocytes. At 24 h after exposure to the ZnO NPs, transmission electron microscopy revealed swelling of the endoplasmic reticulum (ER) and increased numbers of autophagolysosomes in the cultured astrocytes, and increased levels of LC3 (microtubule-associated protein 1 light chain 3)-mediated autophagy were identified by flow cytometry. Apoptosis induced by ZnO NP exposure was confirmed by the elevation of caspase-3/7 activity and 4′,6′-diamidino-2-phenylindole (DAPI) staining. Significant (<i>p</i> < 0.05) changes in the levels of glutathione peroxidase, superoxide dismutase, tumor necrosis factor (TNF-α), and interleukin-6 were observed by enzyme-linked immunoassay (ELISA) assay following the exposure of astrocyte cultures to ZnO NPs. Phosphatidylinositol 3-kinase (PI3K)/mitogen-activated protein kinase (MAPK) dual activation was induced by ZnO NPs in a dose-dependent manner. Additionally, the Akt (protein kinase B) inhibitor BML257 and the mTOR (mammalian target of rapamycin) inhibitor rapamycin contributed to the survival of astrocytes. Inhibitors of cyclooxygenase-2 and lipoxygenase attenuated ZnO NP-induced toxicity. Calcium-modulating compounds, antioxidants, and zinc/iron chelators also decreased ZnO NP-induced toxicity. Together, these results suggest that ZnO NP-induced autophagy and apoptosis may be associated with oxidative stress and the inflammatory process in primary astrocyte cultures.https://www.mdpi.com/2079-4991/9/7/1043astrocyte culturesautophagyapoptosispro-inflammatory cytokineszinc oxide nanoparticles |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Woo-Ju Song Myung-Seon Jeong Dong-Min Choi Kil-Nam Kim Myung-Bok Wie |
spellingShingle |
Woo-Ju Song Myung-Seon Jeong Dong-Min Choi Kil-Nam Kim Myung-Bok Wie Zinc Oxide Nanoparticles Induce Autophagy and Apoptosis via Oxidative Injury and Pro-Inflammatory Cytokines in Primary Astrocyte Cultures Nanomaterials astrocyte cultures autophagy apoptosis pro-inflammatory cytokines zinc oxide nanoparticles |
author_facet |
Woo-Ju Song Myung-Seon Jeong Dong-Min Choi Kil-Nam Kim Myung-Bok Wie |
author_sort |
Woo-Ju Song |
title |
Zinc Oxide Nanoparticles Induce Autophagy and Apoptosis via Oxidative Injury and Pro-Inflammatory Cytokines in Primary Astrocyte Cultures |
title_short |
Zinc Oxide Nanoparticles Induce Autophagy and Apoptosis via Oxidative Injury and Pro-Inflammatory Cytokines in Primary Astrocyte Cultures |
title_full |
Zinc Oxide Nanoparticles Induce Autophagy and Apoptosis via Oxidative Injury and Pro-Inflammatory Cytokines in Primary Astrocyte Cultures |
title_fullStr |
Zinc Oxide Nanoparticles Induce Autophagy and Apoptosis via Oxidative Injury and Pro-Inflammatory Cytokines in Primary Astrocyte Cultures |
title_full_unstemmed |
Zinc Oxide Nanoparticles Induce Autophagy and Apoptosis via Oxidative Injury and Pro-Inflammatory Cytokines in Primary Astrocyte Cultures |
title_sort |
zinc oxide nanoparticles induce autophagy and apoptosis via oxidative injury and pro-inflammatory cytokines in primary astrocyte cultures |
publisher |
MDPI AG |
series |
Nanomaterials |
issn |
2079-4991 |
publishDate |
2019-07-01 |
description |
The present study examined the potential toxic concentrations of zinc oxide nanoparticles (ZnO NPs) and associated autophagy and apoptosis-related injuries in primary neocortical astrocyte cultures. Concentrations of ZnO NPs ≥3 μg/mL induced significant toxicity in the astrocytes. At 24 h after exposure to the ZnO NPs, transmission electron microscopy revealed swelling of the endoplasmic reticulum (ER) and increased numbers of autophagolysosomes in the cultured astrocytes, and increased levels of LC3 (microtubule-associated protein 1 light chain 3)-mediated autophagy were identified by flow cytometry. Apoptosis induced by ZnO NP exposure was confirmed by the elevation of caspase-3/7 activity and 4′,6′-diamidino-2-phenylindole (DAPI) staining. Significant (<i>p</i> < 0.05) changes in the levels of glutathione peroxidase, superoxide dismutase, tumor necrosis factor (TNF-α), and interleukin-6 were observed by enzyme-linked immunoassay (ELISA) assay following the exposure of astrocyte cultures to ZnO NPs. Phosphatidylinositol 3-kinase (PI3K)/mitogen-activated protein kinase (MAPK) dual activation was induced by ZnO NPs in a dose-dependent manner. Additionally, the Akt (protein kinase B) inhibitor BML257 and the mTOR (mammalian target of rapamycin) inhibitor rapamycin contributed to the survival of astrocytes. Inhibitors of cyclooxygenase-2 and lipoxygenase attenuated ZnO NP-induced toxicity. Calcium-modulating compounds, antioxidants, and zinc/iron chelators also decreased ZnO NP-induced toxicity. Together, these results suggest that ZnO NP-induced autophagy and apoptosis may be associated with oxidative stress and the inflammatory process in primary astrocyte cultures. |
topic |
astrocyte cultures autophagy apoptosis pro-inflammatory cytokines zinc oxide nanoparticles |
url |
https://www.mdpi.com/2079-4991/9/7/1043 |
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