ArticleThe Journal of biological chemistry2012
p38α mediates cell survival in response to oxidative stress via induction of antioxidant genes: effect on the p70S6K pathway.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 133 citations in OpenAlex.
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- Tailoring MAPK Pathways: New Therapeutic Avenues for Treating Alzheimer's Disease.Molecular neurobiology · 2025Review
- Understanding Tumor Dormancy: from Experimental Models to Mechanisms and Therapeutic Strategies.Biomolecules & therapeutics · 2025Review
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- Transcriptome-based deep learning analysis identifies drug candidates targeting protein synthesis and autophagy for the treatment of muscle wasting disorder.Experimental & molecular medicine · 2024Article
- The Prolyl Oligopeptidase Inhibitor KYP-2047 Is Cytoprotective and Anti-Inflammatory in Human Retinal Pigment Epithelial Cells with Defective Proteasomal Clearance.Antioxidants (Basel, Switzerland) · 2023Article
- Rickettsial pathogen inhibits tick cell death through tryptophan metabolite mediated activation of p38 MAP kinase.iScience · 2023Article
- mTORC1 beyond anabolic metabolism: Regulation of cell death.The Journal of cell biology · 2022Review
- Free docosahexaenoic acid promotes ferroptotic cell death via lipoxygenase dependent and independent pathways in cancer cells.European journal of nutrition · 2022Article
- HERC2 deficiency activates C-RAF/MKK3/p38 signalling pathway altering the cellular response to oxidative stress.Cellular and molecular life sciences : CMLS · 2022Article
- Pennogenin-3-Pharmaceuticals (Basel, Switzerland) · 2022Article
- ROS and miRNA Dysregulation in Ovarian Cancer Development, Angiogenesis and Therapeutic Resistance.International journal of molecular sciences · 2022Review
- NOS2 andProceedings of the National Academy of Sciences of the United States of America · 2022Article
20 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.