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

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http://hdl.handle.net/10138/317347

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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

Title: Cobalt nanoparticles trigger ferroptosis-like cell death (oxytosis) in neuronal cells : Potential implications for neurodegenerative disease
Author: Gupta, Govind; Gliga, Anda; Hedberg, Jonas; Serra, Angela; Greco, Dario; Odnevall Wallinder, Inger; Fadeel, Bengt
Contributor: University of Helsinki, Institute of Biotechnology
Date: 2020-04
Language: eng
Number of pages: 20
Belongs to series: FASEB Journal
ISSN: 0892-6638
URI: http://hdl.handle.net/10138/317347
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.
Subject: 1182 Biochemistry, cell and molecular biology
cobalt
ferroptosis
hard metal
nanoparticles
neurodegeneration
oxytosis
OXIDATIVE STRESS
MECHANISM
PARTICLES
FORM
TOXICITY
GLUTATHIONE
BIOLOGY
METAL
INDUCED CYTOTOXICITY
HEALTH
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