p38α Mediates Cell Survival in Response to Oxidative Stress via Induction of Antioxidant Genes

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dc.contributor.authorGutiérrez Uzquiza, Álvaro
dc.contributor.authorArechederra, María
dc.contributor.authorBragado Domingo, Paloma
dc.contributor.authorAguirre-Ghiso, Julio A.
dc.contributor.authorPorras Gallo, María Almudena
dc.date.accessioned2024-01-17T08:47:35Z
dc.date.available2024-01-17T08:47:35Z
dc.date.issued2012-01
dc.description.abstractWe reveal a novel pro-survival role for mammalian p38α in response to H(2)O(2), which involves an up-regulation of antioxidant defenses. The presence of p38α increases basal and H(2)O(2)-induced expression of the antioxidant enzymes: superoxide-dismutase 1 (SOD-1), SOD-2, and catalase through different mechanisms, which protects from reactive oxygen species (ROS) accumulation and prevents cell death. p38α was found to regulate (i) H(2)O(2)-induced SOD-2 expression through a direct regulation of transcription mediated by activating transcription factor 2 (ATF-2) and (ii) H(2)O(2)-induced catalase expression through regulation of protein stability and mRNA expression and/or stabilization. As a consequence, SOD and catalase activities are higher in WT MEFs. We also found that this p38α-dependent antioxidant response allows WT cells to maintain an efficient activation of the mTOR/p70S6K pathway. Accordingly, the loss of p38α leads to ROS accumulation in response to H(2)O(2), which causes cell death and inactivation of mTOR/p70S6K signaling. This can be rescued by either p38α re-expression or treatment with the antioxidants, N-acetyl cysteine, or exogenously added catalase. Therefore, our results reveal a novel homeostatic role for p38α in response to oxidative stress, where ROS removal is favored by antioxidant enzymes up-regulation, allowing cell survival and mTOR/p70S6K activation.
dc.description.departmentDepto. de Bioquímica y Biología Molecular
dc.description.facultyFac. de Farmacia
dc.description.refereedTRUE
dc.description.sponsorshipNational Institutes of Health
dc.description.sponsorshipMinisterio de Ciencia, Innovación y Universidades (España)
dc.description.sponsorshipComunidad de Madrid
dc.description.sponsorshipUniversidad Complutense de Madrid
dc.description.sponsorshipSamuel Waxman Cancer Research Foundation Tumor Dormancy
dc.description.sponsorshipNew York Stem Cell Science
dc.description.statuspub
dc.identifier.citationGutiérrez-Uzquiza Á, Arechederra M, Bragado P, Aguirre-Ghiso JA, Porras A. p38α Mediates Cell Survival in Response to Oxidative Stress via Induction of Antioxidant Genes. Journal of Biological Chemistry 2012;287:2632–42. https://doi.org/10.1074/jbc.M111.323709.
dc.identifier.doi10.1074/jbc.m111.323709
dc.identifier.essn1083-351X
dc.identifier.issn0021-9258
dc.identifier.officialurlhttps://doi.org/10.1074/jbc.m111.323709
dc.identifier.urihttps://hdl.handle.net/20.500.14352/93522
dc.issue.number4
dc.journal.titleJournal of Biological Chemistry
dc.language.isoeng
dc.page.final2642
dc.page.initial2632
dc.relation.projectIDinfo:eu-repo/grantAgreement/CA109182
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES017146
dc.relation.projectIDinfo:eu-repo/grantAgreement/FIS-PI070071
dc.relation.projectIDinfo:eu-repo/grantAgreement/SAF-2010-20198-C02-01
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.ucmBiología molecular (Química)
dc.subject.unesco23 Química
dc.titlep38α Mediates Cell Survival in Response to Oxidative Stress via Induction of Antioxidant Genes
dc.typejournal article
dc.type.hasVersionVoR
dc.volume.number287
dspace.entity.typePublication
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