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DC Field | Value | Language |
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dc.contributor.author | Martínez Palacián, Adoración | - |
dc.contributor.author | Castillo, Gaelle del | - |
dc.contributor.author | Suárez Causado, Amileth | - |
dc.contributor.author | García Álvaro, María | - |
dc.contributor.author | Morena Frutos, Diego de la | - |
dc.contributor.author | Fernández, Margarita | - |
dc.contributor.author | Roncero, Cesáreo | - |
dc.contributor.author | Fabregat Romero, Isabel | - |
dc.contributor.author | Herrera, Blanca | - |
dc.contributor.author | Sánchez, Aránzazu | - |
dc.date.accessioned | 2013-04-29T07:53:20Z | - |
dc.date.available | 2013-04-29T07:53:20Z | - |
dc.date.issued | 2013-01-02 | - |
dc.identifier.issn | 1932-6203 | - |
dc.identifier.uri | http://hdl.handle.net/2445/36385 | - |
dc.description.abstract | We 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. | - |
dc.format.extent | 14 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Public Library of Science (PLoS) | - |
dc.relation.isformatof | Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0053108 | - |
dc.relation.ispartof | PLoS One, 2013, vol. 8, num. 1, p. 1-14 | - |
dc.relation.uri | http://dx.doi.org/10.1371/journal.pone.0053108 | - |
dc.rights | cc-by (c) Martínez Palacián, Adoración et al., 2013 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es | - |
dc.source | Articles publicats en revistes (Ciències Fisiològiques) | - |
dc.subject.classification | Apoptosi | - |
dc.subject.classification | Estrès oxidatiu | - |
dc.subject.classification | Cèl·lules hepàtiques | - |
dc.subject.other | Apoptosis | - |
dc.subject.other | Oxidative stress | - |
dc.subject.other | Liver cells | - |
dc.title | Mouse hepatic oval cells require Met-dependent PI3K to impair TGF-β-Induced oxidative stress and apoptosis. | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 621691 | - |
dc.date.updated | 2013-04-29T07:53:20Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 23301029 | - |
Appears in Collections: | Articles publicats en revistes (Ciències Fisiològiques) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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