Cobalt nanoparticles trigger ferroptosis-like cell death (oxytosis) in neuronal cells : Potential implications for neurodegenerative disease

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dc.contributor.author Gupta, Govind
dc.contributor.author Gliga, Anda
dc.contributor.author Hedberg, Jonas
dc.contributor.author Serra, Angela
dc.contributor.author Greco, Dario
dc.contributor.author Odnevall Wallinder, Inger
dc.contributor.author Fadeel, Bengt
dc.date.accessioned 2020-07-03T22:42:04Z
dc.date.available 2020-07-03T22:42:04Z
dc.date.issued 2020-04
dc.identifier.citation Gupta , G , Gliga , A , Hedberg , J , Serra , A , Greco , D , Odnevall Wallinder , I & Fadeel , B 2020 , ' Cobalt nanoparticles trigger ferroptosis-like cell death (oxytosis) in neuronal cells : Potential implications for neurodegenerative disease ' , FASEB Journal , vol. 34 , no. 4 , pp. 5262-5281 . https://doi.org/10.1096/fj.201902191RR
dc.identifier.other PURE: 132788908
dc.identifier.other PURE UUID: 35ae6901-99d0-4d76-8e4d-8bc648468fa2
dc.identifier.other RIS: urn:27C6ED18F3C95A1FA5B9B9CB482A721A
dc.identifier.other WOS: 000515245900001
dc.identifier.other ORCID: /0000-0001-9195-9003/work/76724820
dc.identifier.uri http://hdl.handle.net/10138/317347
dc.description.abstract Abstract The neurotoxicity of hard metal-based nanoparticles (NPs) remains poorly understood. Here, we deployed the human neuroblastoma cell line SH-SY5Y differentiated or not into dopaminergic- and cholinergic-like neurons to study the impact of tungsten carbide (WC) NPs, WC NPs sintered with cobalt (Co), or Co NPs versus soluble CoCl2. Co NPs and Co salt triggered a dose-dependent cytotoxicity with an increase in cytosolic calcium, lipid peroxidation, and depletion of glutathione (GSH). Co NPs and Co salt also suppressed glutathione peroxidase 4 (GPX4) mRNA and protein expression. Co-exposed cells were rescued by N-acetylcysteine (NAC), a precursor of GSH, and partially by liproxstatin-1, an inhibitor of lipid peroxidation. Furthermore, in silico analyses predicted a significant correlation, based on similarities in gene expression profiles, between Co-containing NPs and Parkinson's disease, and changes in the expression of selected genes were validated by RT-PCR. Finally, experiments using primary human dopaminergic neurons demonstrated cytotoxicity and GSH depletion in response to Co NPs and CoCl2 with loss of axonal integrity. Overall, these data point to a marked neurotoxic potential of Co-based but not WC NPs and show that neuronal cell death may occur through a ferroptosis-like mechanism. en
dc.format.extent 20
dc.language.iso eng
dc.relation.ispartof FASEB Journal
dc.rights cc_by_nc_nd
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject 1182 Biochemistry, cell and molecular biology
dc.subject cobalt
dc.subject ferroptosis
dc.subject hard metal
dc.subject nanoparticles
dc.subject neurodegeneration
dc.subject oxytosis
dc.subject OXIDATIVE STRESS
dc.subject MECHANISM
dc.subject PARTICLES
dc.subject FORM
dc.subject TOXICITY
dc.subject GLUTATHIONE
dc.subject BIOLOGY
dc.subject METAL
dc.subject INDUCED CYTOTOXICITY
dc.subject HEALTH
dc.title Cobalt nanoparticles trigger ferroptosis-like cell death (oxytosis) in neuronal cells : Potential implications for neurodegenerative disease en
dc.type Article
dc.contributor.organization Institute of Biotechnology
dc.contributor.organization Research Programs Unit
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1096/fj.201902191RR
dc.relation.issn 0892-6638
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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