ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2009
Regulation of Mn-superoxide dismutase activity and neuroprotection by STAT3 in mice after cerebral ischemia.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 174 citations in OpenAlex.
- Nrf2 and STAT3 Pathways in Protecting Against Methylmercury-Induced Oxidative Stress in Hypothalamic Neuronal GT1-7 Cells.Neurochemical research · 2026Article
- Combined Manganese-Iron Exposure Reduced Oxidative Stress is Associated with the NRF2/NQO1 Pathway in Astrocytic C8-D1A Cells.Biological trace element research · 2026Article
- Reciprocal regulation of GPNMB/HIF-1α for Inhibition of neuronal ferroptosis in delayed encephalopathy after acute carbon monoxide poisoning.Acta neuropathologica communications · 2025Article
- Time course analysis of changes in neuronal loss, oxidative stress, and excitotoxicity in gerbil hippocampus following ischemia and reperfusion under hyperthermic conditions.Histology and histopathology · 2025Article
- Insight into the cardioprotective effects of melatonin: shining a spotlight on intercellular Sirt signaling communication.Molecular and cellular biochemistry · 2025Review
- Activation of sphingosine-1-phosphate receptors can relieve myocardial ischemia-reperfusion injury by mitigating oxidative stress and ferroptosis in cardiomyocytes.International journal of biological sciences · 2025Article
- The antioxidative effect of STAT3 involved in cellular vulnerability to isoflurane.BMC neuroscience · 2024Article
- Neuroprotective effects of intranasal extracellular vesicles from human platelet concentrates supernatants in traumatic brain injury and Parkinson's disease models.Journal of biomedical science · 2024Article
- Rational fusion design inspired by cell-penetrating peptide: SS31/S-14 G Humanin hybrid peptide with amplified multimodal efficacy and bio-permeability for the treatment of Alzheimer's disease.Asian journal of pharmaceutical sciences · 2024Article
- Prolactin is an Endogenous Antioxidant Factor in Astrocytes That Limits Oxidative Stress-Induced Astrocytic Cell Death via the STAT3/NRF2 Signaling Pathway.Neurochemical research · 2024Article
- STAT3 protects dopaminergic neurons against degeneration in animal model of Parkinson's disease.Brain research · 2024Article
- Function and mechanism of the human SOD2 gene in mice cerebral ischemia/ reperfusion injury.Acta cirurgica brasileira · 2024Article
- Astrocytes in intracerebral hemorrhage: impact and therapeutic objectives.Frontiers in molecular neuroscience · 2024Review
- A Comparative Evaluation of Antioxidant Activity of Extract and Essential Oil ofMolecules (Basel, Switzerland) · 2023Article
- Neonatal asphyxia as an inflammatory disease: Reactive oxygen species and cytokines.Frontiers in pediatrics · 2023Review
- STAT3 in medulloblastoma: a key transcriptional regulator and potential therapeutic target.Molecular biology reports · 2022Review
- Role of Endothelial STAT3 in Cerebrovascular Function and Protection from Ischemic Brain Injury.International journal of molecular sciences · 2022Article
- Neuroprotective effects of Korean White ginseng and Red ginseng in an ischemic stroke mouse model.Journal of ginseng research · 2022Article
- Stress Responses as Master Keys to Epigenomic Changes in Transcriptome and Metabolome for Cancer Etiology and Therapeutics.Molecular and cellular biology · 2022Article
- Chlorpromazine and Promethazine (C+P) Reduce Brain Injury after Ischemic Stroke through the PKC-Mediators of inflammation · 2022Article
21 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
Cerebral ischemia and reperfusion increase superoxide anions (O(2)(*-)) in brain mitochondria. Manganese superoxide dismutase (Mn-SOD; SOD2), a primary mitochondrial antioxidant enzyme, scavenges superoxide radicals and its overexpression provides neuroprotection. However, the regulatory mechanism of Mn-SOD expression during cerebral ischemia and reperfusion is still unclear. In this study, we identified the signal transducer and activator of transcription 3 (STAT3) as a transcription factor of the mouse Mn-SOD gene, and elucidated the mechanism of O(2)(*-) overproduction after transient focal cerebral ischemia (tFCI). We found that Mn-SOD expression is significantly reduced by reperfusion in the cerebral ischemic brain. We also found that activated STAT3 is usually recruited into the mouse Mn-SOD promoter and upregulates transcription of the mouse Mn-SOD gene in the normal brain. However, at early postreperfusion periods after tFCI, STAT3 was rapidly downregulated, and its recruitment into the Mn-SOD promoter was completely blocked. In addition, transcriptional activity of the mouse Mn-SOD gene was significantly reduced by STAT3 inhibition in primary cortical neurons. Moreover, we found that STAT3 deactivated by reperfusion induces accumulation of O(2)(*-) in mitochondria. The loss of STAT3 activity induced neuronal cell death by reducing Mn-SOD expression. Using SOD2-/+ heterozygous knock-out mice, we found that Mn-SOD is a direct target of STAT3 in reperfusion-induced neuronal cell death. Our study demonstrates that STAT3 is a novel transcription factor of the mouse Mn-SOD gene and plays a crucial role as a neuroprotectant in regulating levels of reactive oxygen species in the mouse brain.
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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.