ArticleJCI insight
Protein methionine oxidation augments reperfusion injury in acute ischemic stroke.
Article in JCI insight. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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The trial behind it
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- Integrated analysis of the association between methionine cycle and risk of moyamoya disease.CNS neuroscience & therapeutics · 2023Trial
- Astrocytic Redox Homeostasis as a Metabolic Modulator of DNA Damage and Repair in the Ischemic Penumbra.Cells · 2026Review
- Shared metabolomic signatures for prognostic precision across brain injuries.Brain & spine · 2025Article
- Dihydromyricetin regulates RIPK3-CaMKII to prevent necroptosis in high glucose-stimulated cardiomyocytes.Heliyon · 2024Article
- Oxidative Post-translational Protein Modifications upon Ischemia/Reperfusion Injury.Antioxidants (Basel, Switzerland) · 2024Article
- A Metabolomic Signature of Ischemic Stroke Showing Acute Oxidative and Energetic Stress.Antioxidants (Basel, Switzerland) · 2023Article
- Low Glycolysis Is Neuroprotective during Anoxic Spreading Depolarization (SD) and Reoxygenation in Locusts.eNeuro · 2023Article
- The Role of Potential Oxidative Biomarkers in the Prognosis of Acute Ischemic Stroke and the Exploration of Antioxidants as Possible Preventive and Treatment Options.International journal of molecular sciences · 2023Review
- Association between methionine sulfoxide and risk of moyamoya disease.Frontiers in neuroscience · 2023Article
- Redox Mechanisms of Platelet Activation in Aging.Antioxidants (Basel, Switzerland) · 2022Review
- Methionine oxidation of CLK4 promotes the metabolic switch and redox homeostasis in esophageal carcinoma via inhibiting MITF selective autophagy.Clinical and translational medicine · 2022Article
- Role of CaFrontiers in molecular neuroscience · 2022Review
- Transcriptomic and Metabolomic Profiling Reveals the Protective Effect ofFrontiers in pharmacology · 2021Article
- The Antioxidant Role of One-Carbon Metabolism on Stroke.Antioxidants (Basel, Switzerland) · 2020Review
- Metabolic Architecture of Acute Exercise Response in Middle-Aged Adults in the Community.Circulation · 2020Article
- Heat Shock Protein 70 (HSP70) Induction: Chaperonotherapy for Neuroprotection after Brain Injury.Cells · 2020Review
- MsrA Suppresses Inflammatory Activation of Microglia and Oxidative Stress to Prevent Demyelination via Inhibition of the NOX2-MAPKs/NF-κB Signaling Pathway.Drug design, development and therapy · 2020Article
- Loss of methionine sulfoxide reductases increases resistance to oxidative stress.Free radical biology & medicine · 2019Article
- Plasma Oxidized Albumin in Acute Ischemic Stroke Is Associated With Better Outcomes.Frontiers in neurology · 2019Article
- Defective protein repair under methionine sulfoxide A deletion drives autophagy and ARE-dependent gene transcription.Redox biology · 2018Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Reperfusion injury can exacerbate tissue damage in ischemic stroke, but little is known about the mechanisms linking ROS to stroke severity. Here, we tested the hypothesis that protein methionine oxidation potentiates NF-κB activation and contributes to cerebral ischemia/reperfusion injury. We found that overexpression of methionine sulfoxide reductase A (MsrA), an antioxidant enzyme that reverses protein methionine oxidation, attenuated ROS-augmented NF-κB activation in endothelial cells, in part, by protecting against the oxidation of methionine residues in the regulatory domain of calcium/calmodulin-dependent protein kinase II (CaMKII). In a murine model, MsrA deficiency resulted in increased NF-κB activation and neutrophil infiltration, larger infarct volumes, and more severe neurological impairment after transient cerebral ischemia/reperfusion injury. This phenotype was prevented by inhibition of NF-κB or CaMKII. MsrA-deficient mice also exhibited enhanced leukocyte rolling and upregulation of E-selectin, an endothelial NF-κB-dependent adhesion molecule known to contribute to neurovascular inflammation in ischemic stroke. Finally, bone marrow transplantation experiments demonstrated that the neuroprotective effect was mediated by MsrA expressed in nonhematopoietic cells. These findings suggest that protein methionine oxidation in nonmyeloid cells is a key mechanism of postischemic oxidative injury mediated by NF-κB activation, leading to neutrophil recruitment and neurovascular inflammation in acute ischemic stroke.
Identifiers
What OpenQuestion holds
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.