RT Journal Article
T1 p38α Mediates Cell Survival in Response to Oxidative Stress via Induction of Antioxidant Genes
A1 Gutiérrez Uzquiza, Álvaro
A1 Arechederra, María
A1 Bragado Domingo, Paloma
A1 Aguirre-Ghiso, Julio A.
A1 Porras Gallo, María Almudena
AB We 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.
SN 0021-9258
YR 2012
FD 2012-01
LK https://hdl.handle.net/20.500.14352/93522
UL https://hdl.handle.net/20.500.14352/93522
LA eng
NO Gutiérrez-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.
NO National Institutes of Health
NO Ministerio de Ciencia, Innovación y Universidades (España)
NO Comunidad de Madrid
NO Universidad Complutense de Madrid
NO Samuel Waxman Cancer Research Foundation Tumor Dormancy
NO New York Stem Cell Science
DS Docta Complutense
RD 20 abr 2025