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dc.contributor.author Chiappini, Florencia Ana
dc.contributor.author Pontillo, Carolina Andrea
dc.contributor.author Randi, Andrea Silvana
dc.contributor.author Alvarez, Laura
dc.contributor.author Kleiman, Diana Leonor
dc.date.available 2015-08-26T15:44:51Z
dc.date.issued 2013-05-24
dc.identifier.citation Chiappini, Florencia Ana; Pontillo, Carolina Andrea; Randi, Andrea Silvana; Alvarez, Laura; Kleiman, Diana Leonor; Reactive oxygen species and extracellular signal-regulated kinase 1/2 mediate hexachlorobenzene-induced cell death in FRTL-5 rat throyd cells; Oxford University Press; Toxicological Sciences; 134; 2; 24-5-2013; 276-290
dc.identifier.issn 1096-6080
dc.identifier.uri http://hdl.handle.net/11336/1824
dc.description.abstract Hexachlorobenzene (HCB) is an organochlorine pesticide widely distributed in the environment. We have previously shown that chronic HCB exposure triggers apoptosis in rat thyroid follicular cells. This study was carried out to investigate the molecular mechanism by which the pesticide causes apoptosis in FRTL-5 rat thyroid cells exposed to HCB (0.005, 0.05, 0.5, and 5μM) for 2, 6, 8, 24, and 48 h. HCB treatment lowered cell viability and induced apoptotic cell death in a dose- and time-dependent manner, as demonstrated by morphological nuclear changes and the increase of DNA fragmentation. The pesticide increased activation of caspases- 3, -8, and full-length caspase-10 processing. HCB induced mitochondrial membrane depolarization, release of cytochrome c and apoptosis-inducing factor (AIF), from the mitochondria to the cytosol, and AIF nuclear translocation. Cell death was accompanied by an increase in reactive oxygen species (ROS) generation. Blocking of ROS production, with a radical scavenger (Trolox), resulted in inhibition of AIF nuclear translocation and returned cells survival to control levels, demonstrating that ROS are critical mediators of HCB-induced apoptosis. The pesticide increased ERK1/2, JNK, and p38 phosphorylation in a timeand dose-dependent manner. However, when FRTL-5 cells were treated with specific MAPK inhibitors, only blockade of MEK1/2 with PD98059 prevented cell loss of viability, as well as caspase-3 activation. In addition, we demonstrated that HCB-induced production of ROS has a critical role in ERK1/2 activation. These results demonstrate for the first time that HCB induces apoptosis in FRTL-5 cells, by ROS-mediated ERK1/2 activation, through caspase-dependent and -independent pathways.
dc.format application/pdf
dc.language.iso eng
dc.publisher Oxford University Press
dc.rights info:eu-repo/semantics/openAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject HEXACHLOROBENZENE
dc.subject ERK1/2
dc.subject APOPTOSIS
dc.subject REACTIVE OXYGEN SPECIES
dc.subject.classification Bioquímica y Biología Molecular
dc.subject.classification Medicina Básica
dc.subject.classification CIENCIAS MÉDICAS Y DE LA SALUD
dc.title Reactive oxygen species and extracellular signal-regulated kinase 1/2 mediate hexachlorobenzene-induced cell death in FRTL-5 rat throyd cells
dc.type info:eu-repo/semantics/article
dc.type info:ar-repo/semantics/artículo
dc.type info:eu-repo/semantics/publishedVersion
dc.date.updated 2016-03-30 10:35:44.97925-03
dc.journal.volume 134
dc.journal.number 2
dc.journal.pagination 276-290
dc.journal.pais Reino Unido
dc.journal.ciudad Oxford
dc.conicet.avisoEditorial This is a pre-copyedited, author-produced PDF of an article accepted for publication in Toxicological Sciences following peer review. The version of record Chiappini, Florencia Ana; Pontillo, Carolina Andrea; Randi, Andrea Silvana; Alvarez, Laura; Kleiman, Diana Leonor; Reactive oxygen species and extracellular signal-regulated kinase 1/2 mediate hexachlorobenzene-induced cell death in FRTL-5 rat throyd cells; Oxford University Press; Toxicological Sciences; 134; 2; 24-5-2013; 276-290 is available online at: http://dx.doi.org/doi:10.1093/toxsci/kft117
dc.description.fil Fil: Chiappini, Florencia Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina; Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina;
dc.description.fil Fil: Pontillo, Carolina Andrea. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina;
dc.description.fil Fil: Randi, Andrea Silvana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina;
dc.description.fil Fil: Alvarez, Laura. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina;
dc.description.fil Fil: Kleiman, Diana Leonor. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina;
dc.journal.title Toxicological Sciences
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/url/http://toxsci.oxfordjournals.org/content/134/2/276.full.pdf+html
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/doi:10.1093/toxsci/kft117


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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)