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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/72899
Ver los metadatos del registro completo
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oai:ri.conicet.gov.ar:11336/72899 |
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CONICET Digital (CONICET) |
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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 Técnicas2025-09-29T10:17:31Zoai: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:34982025-09-29 10:17:32.203CONICET 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) |
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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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1844614129011130368 |
score |
13.070432 |