Methylmercury-induced developmental toxicity is associated with oxidative stress and cofilin phosphorylation. Cellular and human studies

Autores
Caballero, Beatriz; Olguin, Nair Temis; Campos, Francisco; Farina, Marcelo; Ballester, Ferran; Lopez Espinosa, Maria Jose; Llop, Sabrina; Rodríguez Farré, Eduard; Suñol, Cristina
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Environmental exposure to methylmercury (MeHg) during development is of concern because it is easily incorporated in children's body both pre- and post-natal, it acts at several levels of neural pathways (mitochondria, cytoskeleton, neurotransmission) and it causes behavioral impairment in child. We evaluated the effects of prolonged exposure to 10–600 nM MeHg on primary cultures of mouse cortical (CCN) and of cerebellar granule cells (CGC) during their differentiation period. In addition, it was studied if prenatal MeHg exposure correlated with altered antioxidant defenses and cofilin phosphorylation in human placentas (n = 12) from the INMA cohort (Spain). Exposure to MeHg for 9 days in vitro (DIV) resulted in protein carbonylation and in cell death at concentrations ≥200 nM and ≥300 nM, respectively. Exposure of CCN and CGC to non-cytotoxic MeHg concentrations for 5 DIV induced an early concentration-dependent decrease in cofilin phosphorylation. Furthermore, in both cell types actin was translocated from the cytosol to the mitochondria whereas cofilin translocation was found only in CGC. Translocation of cofilin and actin to mitochondria in CGC occurred from 30 nM MeHg onwards. We also found an increased expression of cortactin and LIMK1 mRNA in CGC but not in CCN. All these effects were prevented by the antioxidant probucol. Cofilin phosphorylation was significantly decreased and a trend for decreased activity of glutathione reductase and glutathione peroxidase was found in the fetal side of human placental samples from the highest (20–40 μg/L) MeHg-exposed group when compared with the low (<7 μg/L) MeHg-exposed group. In summary, cofilin dephosphorylation and oxidative stress are hallmarks of MeHg exposure in both experimental and human systems.
Fil: Caballero, Beatriz. Consejo Superior de Investigaciones Científicas; España
Fil: Olguin, Nair Temis. Consejo Superior de Investigaciones Científicas; España
Fil: Campos, Francisco. Consejo Superior de Investigaciones Científicas; España
Fil: Farina, Marcelo. Universidade Federal de Santa Catarina; Brasil. Consejo Superior de Investigaciones Científicas; España
Fil: Ballester, Ferran. Universidad de Valencia; España. Universitat Jaume I; España
Fil: Lopez Espinosa, Maria Jose. Universidad de Valencia; España. Universitat Jaume I; España
Fil: Llop, Sabrina. Universidad de Valencia; España. Universitat Jaume I; España
Fil: Rodríguez Farré, Eduard. Consejo Superior de Investigaciones Científicas; España
Fil: Suñol, Cristina. Consejo Superior de Investigaciones Científicas; España
Materia
Actin
Cofilin
Cultured Neurons
Human Placenta
Methylmercury
Mitochondria
Oxidative Stress
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/72899
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/72899
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Methylmercury-induced developmental toxicity is associated with oxidative stress and cofilin phosphorylation. Cellular and human studiesCaballero, BeatrizOlguin, Nair TemisCampos, FranciscoFarina, MarceloBallester, FerranLopez Espinosa, Maria JoseLlop, SabrinaRodríguez Farré, EduardSuñol, CristinaActinCofilinCultured NeuronsHuman PlacentaMethylmercuryMitochondriaOxidative Stresshttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Environmental exposure to methylmercury (MeHg) during development is of concern because it is easily incorporated in children's body both pre- and post-natal, it acts at several levels of neural pathways (mitochondria, cytoskeleton, neurotransmission) and it causes behavioral impairment in child. We evaluated the effects of prolonged exposure to 10–600 nM MeHg on primary cultures of mouse cortical (CCN) and of cerebellar granule cells (CGC) during their differentiation period. In addition, it was studied if prenatal MeHg exposure correlated with altered antioxidant defenses and cofilin phosphorylation in human placentas (n = 12) from the INMA cohort (Spain). Exposure to MeHg for 9 days in vitro (DIV) resulted in protein carbonylation and in cell death at concentrations ≥200 nM and ≥300 nM, respectively. Exposure of CCN and CGC to non-cytotoxic MeHg concentrations for 5 DIV induced an early concentration-dependent decrease in cofilin phosphorylation. Furthermore, in both cell types actin was translocated from the cytosol to the mitochondria whereas cofilin translocation was found only in CGC. Translocation of cofilin and actin to mitochondria in CGC occurred from 30 nM MeHg onwards. We also found an increased expression of cortactin and LIMK1 mRNA in CGC but not in CCN. All these effects were prevented by the antioxidant probucol. Cofilin phosphorylation was significantly decreased and a trend for decreased activity of glutathione reductase and glutathione peroxidase was found in the fetal side of human placental samples from the highest (20–40 μg/L) MeHg-exposed group when compared with the low (<7 μg/L) MeHg-exposed group. In summary, cofilin dephosphorylation and oxidative stress are hallmarks of MeHg exposure in both experimental and human systems.Fil: Caballero, Beatriz. Consejo Superior de Investigaciones Científicas; EspañaFil: Olguin, Nair Temis. Consejo Superior de Investigaciones Científicas; EspañaFil: Campos, Francisco. Consejo Superior de Investigaciones Científicas; EspañaFil: Farina, Marcelo. Universidade Federal de Santa Catarina; Brasil. Consejo Superior de Investigaciones Científicas; EspañaFil: Ballester, Ferran. Universidad de Valencia; España. Universitat Jaume I; EspañaFil: Lopez Espinosa, Maria Jose. Universidad de Valencia; España. Universitat Jaume I; EspañaFil: Llop, Sabrina. Universidad de Valencia; España. Universitat Jaume I; EspañaFil: Rodríguez Farré, Eduard. Consejo Superior de Investigaciones Científicas; EspañaFil: Suñol, Cristina. Consejo Superior de Investigaciones Científicas; EspañaElsevier Science2017-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/72899Caballero, Beatriz; Olguin, Nair Temis; Campos, Francisco; Farina, Marcelo; Ballester, Ferran; et al.; Methylmercury-induced developmental toxicity is associated with oxidative stress and cofilin phosphorylation. Cellular and human studies; Elsevier Science; Neurotoxicology; 59; 3-2017; 197-2090161-813XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.neuro.2016.05.018info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0161813X16300961info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:47:45Zoai:ri.conicet.gov.ar:11336/72899instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:47:45.9CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Methylmercury-induced developmental toxicity is associated with oxidative stress and cofilin phosphorylation. Cellular and human studies
title Methylmercury-induced developmental toxicity is associated with oxidative stress and cofilin phosphorylation. Cellular and human studies
spellingShingle Methylmercury-induced developmental toxicity is associated with oxidative stress and cofilin phosphorylation. Cellular and human studies
Caballero, Beatriz
Actin
Cofilin
Cultured Neurons
Human Placenta
Methylmercury
Mitochondria
Oxidative Stress
title_short Methylmercury-induced developmental toxicity is associated with oxidative stress and cofilin phosphorylation. Cellular and human studies
title_full Methylmercury-induced developmental toxicity is associated with oxidative stress and cofilin phosphorylation. Cellular and human studies
title_fullStr Methylmercury-induced developmental toxicity is associated with oxidative stress and cofilin phosphorylation. Cellular and human studies
title_full_unstemmed Methylmercury-induced developmental toxicity is associated with oxidative stress and cofilin phosphorylation. Cellular and human studies
title_sort Methylmercury-induced developmental toxicity is associated with oxidative stress and cofilin phosphorylation. Cellular and human studies
dc.creator.none.fl_str_mv Caballero, Beatriz
Olguin, Nair Temis
Campos, Francisco
Farina, Marcelo
Ballester, Ferran
Lopez Espinosa, Maria Jose
Llop, Sabrina
Rodríguez Farré, Eduard
Suñol, Cristina
author Caballero, Beatriz
author_facet Caballero, Beatriz
Olguin, Nair Temis
Campos, Francisco
Farina, Marcelo
Ballester, Ferran
Lopez Espinosa, Maria Jose
Llop, Sabrina
Rodríguez Farré, Eduard
Suñol, Cristina
author_role author
author2 Olguin, Nair Temis
Campos, Francisco
Farina, Marcelo
Ballester, Ferran
Lopez Espinosa, Maria Jose
Llop, Sabrina
Rodríguez Farré, Eduard
Suñol, Cristina
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Actin
Cofilin
Cultured Neurons
Human Placenta
Methylmercury
Mitochondria
Oxidative Stress
topic Actin
Cofilin
Cultured Neurons
Human Placenta
Methylmercury
Mitochondria
Oxidative Stress
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Environmental exposure to methylmercury (MeHg) during development is of concern because it is easily incorporated in children's body both pre- and post-natal, it acts at several levels of neural pathways (mitochondria, cytoskeleton, neurotransmission) and it causes behavioral impairment in child. We evaluated the effects of prolonged exposure to 10–600 nM MeHg on primary cultures of mouse cortical (CCN) and of cerebellar granule cells (CGC) during their differentiation period. In addition, it was studied if prenatal MeHg exposure correlated with altered antioxidant defenses and cofilin phosphorylation in human placentas (n = 12) from the INMA cohort (Spain). Exposure to MeHg for 9 days in vitro (DIV) resulted in protein carbonylation and in cell death at concentrations ≥200 nM and ≥300 nM, respectively. Exposure of CCN and CGC to non-cytotoxic MeHg concentrations for 5 DIV induced an early concentration-dependent decrease in cofilin phosphorylation. Furthermore, in both cell types actin was translocated from the cytosol to the mitochondria whereas cofilin translocation was found only in CGC. Translocation of cofilin and actin to mitochondria in CGC occurred from 30 nM MeHg onwards. We also found an increased expression of cortactin and LIMK1 mRNA in CGC but not in CCN. All these effects were prevented by the antioxidant probucol. Cofilin phosphorylation was significantly decreased and a trend for decreased activity of glutathione reductase and glutathione peroxidase was found in the fetal side of human placental samples from the highest (20–40 μg/L) MeHg-exposed group when compared with the low (<7 μg/L) MeHg-exposed group. In summary, cofilin dephosphorylation and oxidative stress are hallmarks of MeHg exposure in both experimental and human systems.
Fil: Caballero, Beatriz. Consejo Superior de Investigaciones Científicas; España
Fil: Olguin, Nair Temis. Consejo Superior de Investigaciones Científicas; España
Fil: Campos, Francisco. Consejo Superior de Investigaciones Científicas; España
Fil: Farina, Marcelo. Universidade Federal de Santa Catarina; Brasil. Consejo Superior de Investigaciones Científicas; España
Fil: Ballester, Ferran. Universidad de Valencia; España. Universitat Jaume I; España
Fil: Lopez Espinosa, Maria Jose. Universidad de Valencia; España. Universitat Jaume I; España
Fil: Llop, Sabrina. Universidad de Valencia; España. Universitat Jaume I; España
Fil: Rodríguez Farré, Eduard. Consejo Superior de Investigaciones Científicas; España
Fil: Suñol, Cristina. Consejo Superior de Investigaciones Científicas; España
description Environmental exposure to methylmercury (MeHg) during development is of concern because it is easily incorporated in children's body both pre- and post-natal, it acts at several levels of neural pathways (mitochondria, cytoskeleton, neurotransmission) and it causes behavioral impairment in child. We evaluated the effects of prolonged exposure to 10–600 nM MeHg on primary cultures of mouse cortical (CCN) and of cerebellar granule cells (CGC) during their differentiation period. In addition, it was studied if prenatal MeHg exposure correlated with altered antioxidant defenses and cofilin phosphorylation in human placentas (n = 12) from the INMA cohort (Spain). Exposure to MeHg for 9 days in vitro (DIV) resulted in protein carbonylation and in cell death at concentrations ≥200 nM and ≥300 nM, respectively. Exposure of CCN and CGC to non-cytotoxic MeHg concentrations for 5 DIV induced an early concentration-dependent decrease in cofilin phosphorylation. Furthermore, in both cell types actin was translocated from the cytosol to the mitochondria whereas cofilin translocation was found only in CGC. Translocation of cofilin and actin to mitochondria in CGC occurred from 30 nM MeHg onwards. We also found an increased expression of cortactin and LIMK1 mRNA in CGC but not in CCN. All these effects were prevented by the antioxidant probucol. Cofilin phosphorylation was significantly decreased and a trend for decreased activity of glutathione reductase and glutathione peroxidase was found in the fetal side of human placental samples from the highest (20–40 μg/L) MeHg-exposed group when compared with the low (<7 μg/L) MeHg-exposed group. In summary, cofilin dephosphorylation and oxidative stress are hallmarks of MeHg exposure in both experimental and human systems.
publishDate 2017
dc.date.none.fl_str_mv 2017-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/72899
Caballero, Beatriz; Olguin, Nair Temis; Campos, Francisco; Farina, Marcelo; Ballester, Ferran; et al.; Methylmercury-induced developmental toxicity is associated with oxidative stress and cofilin phosphorylation. Cellular and human studies; Elsevier Science; Neurotoxicology; 59; 3-2017; 197-209
0161-813X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/72899
identifier_str_mv Caballero, Beatriz; Olguin, Nair Temis; Campos, Francisco; Farina, Marcelo; Ballester, Ferran; et al.; Methylmercury-induced developmental toxicity is associated with oxidative stress and cofilin phosphorylation. Cellular and human studies; Elsevier Science; Neurotoxicology; 59; 3-2017; 197-209
0161-813X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.neuro.2016.05.018
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0161813X16300961
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science
publisher.none.fl_str_mv Elsevier Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.982451

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