“Iron free” zinc oxide nanoparticles with ion-leaking properties disrupt intracellular ROS and iron homeostasis to induce ferroptosis
Identifieur interne : 000005 ( an2020/Analysis ); précédent : 000004; suivant : 000006“Iron free” zinc oxide nanoparticles with ion-leaking properties disrupt intracellular ROS and iron homeostasis to induce ferroptosis
Auteurs : Changping Zhang [République populaire de Chine] ; Zixuan Liu [République populaire de Chine] ; Yuhao Zhang [République populaire de Chine] ; Liang Ma [République populaire de Chine] ; Erqun Song [République populaire de Chine] ; Yang Song [République populaire de Chine]Source :
- Cell Death & Disease [ 2041-4889 ] ; 2020.
Abstract
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.
Url:
DOI: 10.1038/s41419-020-2384-5
PubMed: 32170066
PubMed Central: 7070056
Affiliations:
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Chemistry (Southwest University), Ministry of Education, College of Food Science,</institution><institution>Southwest University,</institution></institution-wrap>Chongqing, 400715 People’s Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chongqing</wicri:regionArea></affiliation></author><author><name sortKey="Liu, Zixuan" sort="Liu, Zixuan" uniqKey="Liu Z" first="Zixuan" last="Liu">Zixuan Liu</name><affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.263906.8</institution-id><institution>Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences,</institution><institution>Southwest University,</institution></institution-wrap>Chongqing, 400715 People’s Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chongqing</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, Yuhao" sort="Zhang, Yuhao" uniqKey="Zhang Y" first="Yuhao" last="Zhang">Yuhao Zhang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.263906.8</institution-id><institution>Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Food Science,</institution><institution>Southwest University,</institution></institution-wrap>Chongqing, 400715 People’s Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chongqing</wicri:regionArea></affiliation></author><author><name sortKey="Ma, Liang" sort="Ma, Liang" uniqKey="Ma L" first="Liang" last="Ma">Liang Ma</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id 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Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chongqing</wicri:regionArea></affiliation></author><author><name sortKey="Song, Yang" sort="Song, Yang" uniqKey="Song Y" first="Yang" last="Song">Yang Song</name><affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="GRID">grid.263906.8</institution-id><institution>Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences,</institution><institution>Southwest University,</institution></institution-wrap>Chongqing, 400715 People’s Republic of China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Chongqing</wicri:regionArea></affiliation></author></analytic><series><title level="j">Cell Death & Disease</title><idno type="eISSN">2041-4889</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="Par1">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.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Zhao, F" uniqKey="Zhao F">F Zhao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nel, A" uniqKey="Nel A">A Nel</name></author><author><name sortKey="Xia, T" uniqKey="Xia T">T Xia</name></author><author><name sortKey="Madler, L" uniqKey="Madler L">L Madler</name></author><author><name sortKey="Li, N" uniqKey="Li N">N Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Galluzzi, L" uniqKey="Galluzzi L">L Galluzzi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dixon, Sj" uniqKey="Dixon S">SJ Dixon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dixon, Sj" uniqKey="Dixon S">SJ Dixon</name></author><author><name 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Cherian</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pagani, Ma" uniqKey="Pagani M">MA Pagani</name></author><author><name sortKey="Casamayor, A" uniqKey="Casamayor A">A Casamayor</name></author><author><name sortKey="Serrano, R" uniqKey="Serrano R">R Serrano</name></author><author><name sortKey="Atrian, S" uniqKey="Atrian S">S Atrian</name></author><author><name sortKey="Arino, J" uniqKey="Arino J">J Arino</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Zhang, Changping" sort="Zhang, Changping" uniqKey="Zhang C" first="Changping" last="Zhang">Changping Zhang</name></noRegion><name sortKey="Liu, Zixuan" sort="Liu, Zixuan" uniqKey="Liu Z" first="Zixuan" last="Liu">Zixuan Liu</name><name sortKey="Ma, Liang" sort="Ma, Liang" uniqKey="Ma L" first="Liang" last="Ma">Liang Ma</name><name sortKey="Song, Erqun" sort="Song, Erqun" uniqKey="Song E" first="Erqun" last="Song">Erqun Song</name><name sortKey="Song, Yang" sort="Song, Yang" uniqKey="Song Y" first="Yang" last="Song">Yang Song</name><name sortKey="Zhang, Yuhao" sort="Zhang, Yuhao" uniqKey="Zhang Y" first="Yuhao" last="Zhang">Yuhao Zhang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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