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“Iron free” zinc oxide nanoparticles with ion-leaking properties disrupt intracellular ROS and iron homeostasis to induce ferroptosis

Exposure to nanomaterials (NMs) is an emerging threat to human health, and the understanding of their intracellular behavior and related toxic effects is urgently needed. Ferroptosis is a newly discovered, iron-mediated cell death that is distinctive from apoptosis or other cell-death pathways. No e...

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Autores principales: Zhang, Changping, Liu, Zixuan, Zhang, Yuhao, Ma, Liang, Song, Erqun, Song, Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7070056/
https://www.ncbi.nlm.nih.gov/pubmed/32170066
http://dx.doi.org/10.1038/s41419-020-2384-5
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author Zhang, Changping
Liu, Zixuan
Zhang, Yuhao
Ma, Liang
Song, Erqun
Song, Yang
author_facet Zhang, Changping
Liu, Zixuan
Zhang, Yuhao
Ma, Liang
Song, Erqun
Song, Yang
author_sort Zhang, Changping
collection PubMed
description Exposure to nanomaterials (NMs) is an emerging threat to human health, and the understanding of their intracellular behavior and related toxic effects is urgently needed. Ferroptosis is a newly discovered, iron-mediated cell death that is distinctive from apoptosis or other cell-death pathways. No evidence currently exists for the effect of “iron free” engineered NMs on ferroptosis. We showed by several approaches that (1) zinc oxide nanoparticles (ZnO NPs)-induced cell death involves ferroptosis; (2) ZnO NPs-triggered ferroptosis is associated with elevation of reactive oxygen species (ROS) and lipid peroxidation, along with depletion of glutathione (GSH) and downregulation of glutathione peroxidase 4 (GPx4); (3) ZnO NPs disrupt intracellular iron homeostasis by orchestrating iron uptake, storage and export; (4) p53 largely participates in ZnO NPs-induced ferroptosis; and (5) ZnO particle remnants and dissolved zinc ion both contribute to ferroptosis. In conclusion, our data provide a new mechanistic rationale for ferroptosis as a novel cell-death phenotype induced by engineered NMs.
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spelling pubmed-70700562020-03-18 “Iron free” zinc oxide nanoparticles with ion-leaking properties disrupt intracellular ROS and iron homeostasis to induce ferroptosis Zhang, Changping Liu, Zixuan Zhang, Yuhao Ma, Liang Song, Erqun Song, Yang Cell Death Dis Article Exposure to nanomaterials (NMs) is an emerging threat to human health, and the understanding of their intracellular behavior and related toxic effects is urgently needed. Ferroptosis is a newly discovered, iron-mediated cell death that is distinctive from apoptosis or other cell-death pathways. No evidence currently exists for the effect of “iron free” engineered NMs on ferroptosis. We showed by several approaches that (1) zinc oxide nanoparticles (ZnO NPs)-induced cell death involves ferroptosis; (2) ZnO NPs-triggered ferroptosis is associated with elevation of reactive oxygen species (ROS) and lipid peroxidation, along with depletion of glutathione (GSH) and downregulation of glutathione peroxidase 4 (GPx4); (3) ZnO NPs disrupt intracellular iron homeostasis by orchestrating iron uptake, storage and export; (4) p53 largely participates in ZnO NPs-induced ferroptosis; and (5) ZnO particle remnants and dissolved zinc ion both contribute to ferroptosis. In conclusion, our data provide a new mechanistic rationale for ferroptosis as a novel cell-death phenotype induced by engineered NMs. Nature Publishing Group UK 2020-03-13 /pmc/articles/PMC7070056/ /pubmed/32170066 http://dx.doi.org/10.1038/s41419-020-2384-5 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Zhang, Changping
Liu, Zixuan
Zhang, Yuhao
Ma, Liang
Song, Erqun
Song, Yang
“Iron free” zinc oxide nanoparticles with ion-leaking properties disrupt intracellular ROS and iron homeostasis to induce ferroptosis
title “Iron free” zinc oxide nanoparticles with ion-leaking properties disrupt intracellular ROS and iron homeostasis to induce ferroptosis
title_full “Iron free” zinc oxide nanoparticles with ion-leaking properties disrupt intracellular ROS and iron homeostasis to induce ferroptosis
title_fullStr “Iron free” zinc oxide nanoparticles with ion-leaking properties disrupt intracellular ROS and iron homeostasis to induce ferroptosis
title_full_unstemmed “Iron free” zinc oxide nanoparticles with ion-leaking properties disrupt intracellular ROS and iron homeostasis to induce ferroptosis
title_short “Iron free” zinc oxide nanoparticles with ion-leaking properties disrupt intracellular ROS and iron homeostasis to induce ferroptosis
title_sort “iron free” zinc oxide nanoparticles with ion-leaking properties disrupt intracellular ros and iron homeostasis to induce ferroptosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7070056/
https://www.ncbi.nlm.nih.gov/pubmed/32170066
http://dx.doi.org/10.1038/s41419-020-2384-5
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