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Cytoplasmic aggregation of uranium in human dopaminergic cells after continuous exposure to soluble uranyl at non-cytotoxic concentrations

hal.structure.identifierCentre d'Etudes Nucléaires de Bordeaux Gradignan [CENBG]
dc.contributor.authorCARMONA, Asuncion
hal.structure.identifierCentre d'Etudes Nucléaires de Bordeaux Gradignan [CENBG]
dc.contributor.authorPORCARO, Francesco
hal.structure.identifierSynchrotron SOLEIL [SSOLEIL]
dc.contributor.authorSOMOGYI, Andrea
hal.structure.identifierCentre d'Etudes Nucléaires de Bordeaux Gradignan [CENBG]
dc.contributor.authorROUDEAU, Stéphane
hal.structure.identifierCentre d'Etudes Nucléaires de Bordeaux Gradignan [CENBG]
dc.contributor.authorDOMART, Florelle
hal.structure.identifierSynchrotron SOLEIL [SSOLEIL]
dc.contributor.authorMEDJOUBI, Kadda
hal.structure.identifierService d'études analytiques et de réactivité des surfaces [SEARS]
dc.contributor.authorAUBERT, Michel
hal.structure.identifierService d'études analytiques et de réactivité des surfaces [SEARS]
dc.contributor.authorISNARD, Hélène
hal.structure.identifierService d'études analytiques et de réactivité des surfaces [SEARS]
dc.contributor.authorNONELL, Anthony
hal.structure.identifierService d'études analytiques et de réactivité des surfaces [SEARS]
dc.contributor.authorRINCEL, Anaïs
hal.structure.identifierService d'études analytiques et de réactivité des surfaces [SEARS]
dc.contributor.authorPAREDES, Eduardo
hal.structure.identifierInstitut de Biosciences et Biotechnologies d'Aix-Marseille (ex-IBEB) [BIAM]
dc.contributor.authorVIDAUD, Claude
hal.structure.identifierInstitut de Biosciences et Biotechnologies d'Aix-Marseille (ex-IBEB) [BIAM]
hal.structure.identifierInteractions Protéine Métal [IPM]
dc.contributor.authorMALARD, Veronique
hal.structure.identifierService d'études analytiques et de réactivité des surfaces [SEARS]
dc.contributor.authorBRESSON, Carole
hal.structure.identifierCentre d'Etudes Nucléaires de Bordeaux Gradignan [CENBG]
dc.contributor.authorORTEGA, Richard
dc.date.issued2021
dc.identifier.issn0161-813X
dc.description.abstractEnUranium exposure can lead to neurobehavioral alterations in particular of the monoaminergic system, even at non-cytotoxic concentrations. However, the mechanisms of uranium neurotoxicity after non-cytotoxic exposure are still poorly understood. In particular, imaging uranium in neurons at low intracellular concentration is still very challenging. We investigated uranium intracellular localization by means of synchrotron X-ray fluorescence imaging with high spatial resolution (< 300 nm) and high analytical sensitivity (< 1 μg.g -1 per 300 nm pixel). Neuron-like SH-SY5Y human cells differentiated into a dopaminergic phenotype were continuously exposed, for seven days, to a non-cytotoxic concentration (10 μM) of soluble natural uranyl. Cytoplasmic submicron uranium aggregates were observed accounting on average for 62% of the intracellular uranium content. In some aggregates, uranium and iron were co-localized suggesting common metabolic pathways between uranium and iron storage. Uranium aggregates contained no calcium or phosphorous indicating that detoxification mechanisms in neuron-like cells are different from those described in bone or kidney cells. Uranium intracellular distribution was compared to fluorescently labeled organelles (lysosomes, early and late endosomes) and to fetuin-A, a high affinity uranium-binding protein. A strict correlation could not be evidenced between uranium and the labelled organelles, or with vesicles containing fetuin-A. Our results indicate a new mechanism of uranium cytoplasmic aggregation after non-cytotoxic uranyl exposure that could be involved in neuronal defense through uranium sequestration into less reactive species. The remaining soluble fraction of uranium would be responsible for protein binding and the resulting neurotoxic effects.
dc.language.isoen
dc.publisherElsevier
dc.title.enCytoplasmic aggregation of uranium in human dopaminergic cells after continuous exposure to soluble uranyl at non-cytotoxic concentrations
dc.typeArticle de revue
dc.identifier.doi10.1016/j.neuro.2020.10.015
dc.subject.halChimie/Chimie analytique
bordeaux.journalNeuroToxicology
bordeaux.page35-44
bordeaux.volume82
bordeaux.peerReviewedoui
hal.identifierhal-03066343
hal.version1
hal.popularnon
hal.audienceInternationale
hal.origin.linkhttps://hal.archives-ouvertes.fr//hal-03066343v1
bordeaux.COinSctx_ver=Z39.88-2004&amp;rft_val_fmt=info:ofi/fmt:kev:mtx:journal&amp;rft.jtitle=NeuroToxicology&amp;rft.date=2021&amp;rft.volume=82&amp;rft.spage=35-44&amp;rft.epage=35-44&amp;rft.eissn=0161-813X&amp;rft.issn=0161-813X&amp;rft.au=CARMONA,%20Asuncion&amp;PORCARO,%20Francesco&amp;SOMOGYI,%20Andrea&amp;ROUDEAU,%20St%C3%A9phane&amp;DOMART,%20Florelle&amp;rft.genre=article


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