ArticlePloS one2013
ROS detoxification and proinflammatory cytokines are linked by p38 MAPK signaling in a model of mature astrocyte activation.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
39 citing papers in PubMed, 65 citations in OpenAlex.
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- Astrocyte Biology in CNS Inflammatory Diseases: A Clinical-Translational Perspective.Neurology(R) neuroimmunology & neuroinflammation · 2026Review
- Beyond Radical Scavengers: Focus on NADPH Oxidases (NOX) Inhibitors as New Agents for Antioxidant Therapy in Alzheimer's Disease.Antioxidants (Basel, Switzerland) · 2025Review
- The Effects of Antioxidant Approved Drugs and Under Investigation Compounds with Potential of Improving Sleep Disorders and their Associated Comorbidities Associated with Oxidative Stress and Inflammation.Mini reviews in medicinal chemistry · 2025Review
- p38α Mitogen-Activated Protein Kinase-An Emerging Drug Target for the Treatment of Alzheimer's Disease.Molecules (Basel, Switzerland) · 2024Review
- Protective Effects of Lipoxin AbioRxiv : the preprint server for biology · 2024Article
- Lipoxins AJournal of neuroinflammation · 2024Article
- The Roles of Caloric Restriction Mimetics in Central Nervous System Demyelination and Remyelination.Current issues in molecular biology · 2023Review
- Rapid isolation of intact retinal astrocytes: a novel approach.Acta neuropathologica communications · 2023Article
- New Insights on Dietary Polyphenols for the Management of Oxidative Stress and Neuroinflammation in Diabetic Retinopathy.Antioxidants (Basel, Switzerland) · 2023Review
- Targeting neuroinflammation in Alzheimer's disease: from mechanisms to clinical applications.Neural regeneration research · 2023Review
- Alteration of Mesenchymal Stem Cells Isolated from Glioblastoma Multiforme under the Influence of Photodynamic Treatment.Current issues in molecular biology · 2023Article
- A review of cytokine-based pathophysiology of Long COVID symptoms.Frontiers in medicine · 2023Article
- Nattokinase attenuates bisphenol A or gamma irradiation-mediated hepatic and neural toxicity by activation of Nrf2 and suppression of inflammatory mediators in rats.Environmental science and pollution research international · 2022Article
- Evidence of an Annexin A4 mediated plasma membrane repair response to biomechanical strain associated with glaucoma pathogenesis.Journal of cellular physiology · 2022Article
- Astrocyte Mitochondria in White-Matter Injury.Neurochemical research · 2021Review
- Mesenchymal Stem Cells Ameliorate Cuprizone-Induced Demyelination by Targeting Oxidative Stress and Mitochondrial Dysfunction.Cellular and molecular neurobiology · 2021Article
- Beyond the GFAP-Astrocyte Protein Markers in the Brain.Biomolecules · 2021Review
- Exposure to 2.45 GHz Radiation Triggers Changes in HSP-70, Glucocorticoid Receptors and GFAP Biomarkers in Rat Brain.International journal of molecular sciences · 2021Article
- Cytokine changes in fatal cases of paraquat poisoning.American journal of translational research · 2021Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Astrocytes are the most abundant glial cell in the retinal nerve fiber layer (NFL) and optic nerve head (ONH), and perform essential roles in maintaining retinal ganglion cell (RGC) detoxification and homeostasis. Mature astrocytes are relatively quiescent, but rapidly undergo a phenotypic switch in response to insult, characterized by upregulation of intermediate filament proteins, loss of glutamate buffering, secretion of pro-inflammatory cytokines, and increased antioxidant production. These changes result in both positive and negative influences on RGCs. However, the mechanism regulating these responses is still unclear, and pharmacologic strategies to modulate select aspects of this switch have not been thoroughly explored. Here we describe a system for rapid culture of mature astrocytes from the adult rat retina that remain relatively quiescent, but respond robustly when challenged with oxidative damage, a key pathogenic stress associated with inner retinal injury. When primary astrocytes were exposed to reactive oxygen species (ROS) we consistently observed characteristic changes in activation markers, along with increased expression of detoxifying genes, and secretion of proinflammatory cytokines. This in vitro model was then used for a pilot chemical screen to target specific aspects of this switch. Increased activity of p38α and β Mitogen Activated Protein Kinases (MAPKs) were identified as a necessary signal regulating expression of MnSOD, and heme oxygenase 1 (HO-1), with consequent changes in ROS-mediated injury. Additionally, multiplex cytokine profiling detected p38 MAPK-dependent secretion of IL-6, MCP-1, and MIP-2α, which are proinflammatory signals recently implicated in damage to the inner retina. These data provide a mechanism to link increased oxidative stress to proinflammatory signaling by astrocytes, and establish this assay as a useful model to further dissect factors regulating the reactive switch.
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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.