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dc.contributor.authorBriz, Víctor-
dc.contributor.authorMolina-Molina, José-Manuel-
dc.contributor.authorSánchez-Redondo, Sara-
dc.contributor.authorFernández, Marieta-
dc.contributor.authorGrimalt, Joan O.-
dc.contributor.authorOlea, Nicolás-
dc.contributor.authorRodríguez-Farré, Eduard-
dc.contributor.authorSuñol, Cristina-
dc.date.accessioned2013-05-06T12:01:24Z-
dc.date.available2013-05-06T12:01:24Z-
dc.date.issued2011-
dc.identifierissn: 1096-6080-
dc.identifiere-issn: 1096-0929-
dc.identifier.citationToxicological Sciences 120(2): 413-427 (2011)-
dc.identifier.urihttp://hdl.handle.net/10261/75550-
dc.descriptionEl pdf del artículo es la versión post-print.-
dc.description.abstractThe organochlorine chemicals endosulfan, dieldrin, and γ-hexachlorocyclohexane (lindane) are persistent pesticides to which people are exposed mainly via diet. Their antagonism of the γ-aminobutyric acid-A (GABAA) receptor makes them convulsants. They are also endocrine disruptors because of their interaction with the estrogen receptor (ER). Here, we study the effects of dieldrin, endosulfan, and lindane on ERs in primary cultures of cortical neurons (CN) and cerebellar granule cells (CGC). All the compounds tested inhibited the binding of [3H]-estradiol to the ER in both CN and CGC, with dieldrin in CGC showing the highest affinity. We also determined the effects of the pesticides on protein kinase B (Akt) and extracellular-regulated kinase 1 and 2 (ERK1/2) phosphorylation. Dieldrin and endosulfan increased Akt phosphorylation in CN, which was inhibited by the ERb antagonist 4-[2-phenyl-5,7-bis(trifluoromethyl)pyrazolo[1,5-α]pyrimidin-3-yl]phenol. Instead, Akt and ERK1/2 phosphorylation induced by dieldrin in CGC was mediated by multiple activation of ERa, ERb, and G protein- coupled receptor 30. Lindane did not activate these pathways, but it inhibited estradiol-mediated Akt and ERK1/2 activation. In CN, all the chemicals activated ERK1/2 through a mechanism involving GABAA and glutamate receptors. Long-term exposure to these pesticides reduced the levels of ERα, but not of ERβ. Moreover, extracts of CN treated with endosulfan, dieldrin, or lindane induced cell proliferation in MCF-7 human breast cancer-derived cells, whereas only extracts of CGC treated with dieldrin induced MCF-7 cell proliferation. Overall, the observed alterations on ER-mediated signaling and ER levels in neurons might contribute to the neurotoxicity of these organochlorine pesticides. © The Author 2011. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved.-
dc.description.sponsorshipThis research was supported by grants from Ministry of Health (FIS 061212, FIS10/0453), CIBERESP (AA08-001), Generalitat de Catalunya (2009/SGR/214) and from Consejería de Innovación, Ciencia y Empresa de la Junta de Andalucía (P09-CTS-5488).-
dc.language.isoeng-
dc.publisherOxford University Press-
dc.relation.isversionofPostprint-
dc.rightsopenAccess-
dc.titleDifferential estrogenic effects of the persistent organochlorine pesticides dieldrin, endosulfan, and lindane in primary neuronal cultures-
dc.typeartículo-
dc.identifier.doi10.1093/toxsci/kfr019-
dc.relation.publisherversionhttp://dx.doi.org/10.1093/toxsci/kfr019-
dc.date.updated2013-05-06T12:01:24Z-
dc.description.versionPeer Reviewed-
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