1. DIGITAL.CSIC
  2. Biología y Biomedicina
  3. Instituto de Investigaciones Biomédicas Sols-Morreale (IIBM)
  4. (IIBM) Artículos
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/77434
COMPARTIR / EXPORTAR:
logo share SHARE logo core CORE BASE

Comparte tu historia
de Acceso Abierto
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE

Invitar a revisión por pares abierta
Campo DC Valor Lengua/Idioma
dc.contributor.authorCastillo, Gaelle del-
dc.contributor.authorHerrera, Blanca-
dc.contributor.authorSánchez, Aránzazu-
dc.date.accessioned2013-06-04T08:38:05Z-
dc.date.available2013-06-04T08:38:05Z-
dc.date.issued2013-
dc.identifierdoi: 10.1371/journal.pone.0053108-
dc.identifierissn: 1932-6203-
dc.identifier.citationPLoS ONE 8(1): e53108 (2013)-
dc.identifier.urihttp://hdl.handle.net/10261/77434-
dc.descriptionThis is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.-
dc.description.abstractWe have previously shown that oval cells harboring a genetically inactivated Met tyrosine kinase (Met-/- oval cells) are more sensitive to TGF-β-induced apoptosis than cells expressing a functional Met (Metflx/flx), demonstrating that the HGF/Met axis plays a pivotal role in oval cell survival. Here, we have examined the mechanism behind this effect and have found that TGF-β induced a mitochondria-dependent apoptotic cell death in Metflx/flx and Met-/- oval cells, associated with a marked increase in levels of the BH3-only proteins Bim and Bmf. Bmf plays a key role during TGF-β-mediated apoptosis since knocking down of BMF significantly diminished the apoptotic response in Met-/- oval cells. TGF-β also induced oxidative stress accompanied by NADPH oxidase 4 (Nox4) mRNA up-regulation and decreased protein levels of antioxidant enzymes. Antioxidants inhibit both TGF-β-induced caspase 3 activity and Bmf up-regulation, revealing an oxidative stress-dependent Bmf regulation by TGF-β. Notably, oxidative stress-related events were strongly amplified in Met-/- oval cells, emphasizing the critical role of Met in promoting survival. Pharmacological inhibition of PI3K did impair HGF-driven protection from TGF-β-induced apoptosis and increased sensitivity of Metflx/flx oval cells to TGF-ß by enhancing oxidative stress, reaching apoptotic indices similar to those obtained in Met-/- oval cells. Interestingly, both PI3K inhibition and/or knockdown itself resulted in caspase-3 activation and loss of viability in Metflx/flx oval cells, whereas no effect was observed in Met-/- oval cells. Altogether, results presented here provide solid evidences that both paracrine and autocrine HGF/Met signaling requires PI3K to promote mouse hepatic oval cell survival against TGF-β-induced oxidative stress and apoptosis. © 2013 Martínez-Palacián et al.-
dc.description.sponsorshipAMP was recipient of a research-training contract (grant SAF2006-12025) from the Ministry of Education and Science. GC was recipient of a researchtraining contract from the Ministry of Education and Science. ASC was recipient of an Alban scholarship program and then a research assistant contract (grant SAF2009-12477). MGA is recipient of a research assistant contract (grant S2010/BMD-2402). This work has been supported by grants SAF2006-12025 from Ministry of Education and Science (Spain), SAF2009-12477 from Ministry of Science and Innovation (Spain), and 920359 (CAM-UCM, BSCH-UCM).-
dc.language.isoeng-
dc.publisherPublic Library of Science-
dc.relationS2010/BMD-2402/MITOLAB-
dc.relation.isversionofPublisher's version-
dc.relation.isversionofPublisher's version-
dc.rightsopenAccess-
dc.titleMouse hepatic oval cells require met-dependent PI3K to impair TGF-β-induced oxidative stress and apoptosis-
dc.typeartículo-
dc.identifier.doi10.1371/journal.pone.0053108-
dc.relation.publisherversionhttp://dx.doi.org/10.1371/journal.pone.0053108-
dc.date.updated2013-06-04T08:38:05Z-
dc.description.versionPeer Reviewed-
dc.rights.licensehttp://creativecommons.org/licenses/by/4.0/-
dc.contributor.funderComunidad de Madrid-
dc.contributor.funderMinisterio de Educación y Ciencia (España)-
dc.contributor.funderMinisterio de Ciencia e Innovación (España)-
dc.contributor.funderUniversidad Complutense de Madrid-
dc.contributor.funderBanco Santander-
dc.relation.csicSí-
dc.identifier.funderhttp://dx.doi.org/10.13039/501100004837es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100002911es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/100010784es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/100012818es_ES
dc.identifier.pmid23301029-
dc.type.coarhttp://purl.org/coar/resource_type/c_6501es_ES
item.grantfulltextopen-
item.cerifentitytypePublications-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.languageiso639-1en-
item.fulltextWith Fulltext-
item.openairetypeartículo-
Aparece en las colecciones: (IIBM) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato
Mouse Hepatic.pdf910,27 kBAdobe PDFVista previa
Visualizar/Abrir
Show simple item record

CORE Recommender

PubMed Central
Citations

17
checked on 13-abr-2024

SCOPUSTM   
Citations

25
checked on 15-abr-2024

WEB OF SCIENCETM
Citations

22
checked on 24-feb-2024

Page view(s)

345
checked on 16-abr-2024

Download(s)

216
checked on 16-abr-2024

Google ScholarTM

Check

Altmetric

Altmetric


Artículos relacionados:


Este item está licenciado bajo una Licencia Creative Commons Creative Commons