ArticleAntioxidants & redox signaling2014
Nitrosative stress induces peroxiredoxin 1 ubiquitination during ischemic insult via E6AP activation in endothelial cells both in vitro and in vivo.
Article in Antioxidants & redox signaling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- In Vitro Oxygen Glucose Deprivation Model of Ischemic Stroke: A Proteomics-Driven Systems Biological Perspective.Molecular neurobiology · 2022Pooled it
- Peroxiredoxins in Stroke: Friends and Foes.Cells · 2026Review
- Moonlighting Functions of Mammalian Peroxiredoxins in Cellular Signaling.Antioxidants (Basel, Switzerland) · 2026Review
- The role of remote ischemic conditioning in ischemic stroke: neuroprotective mechanisms and future directions.Frontiers in immunology · 2026Review
- Microcirculatory failure after successful recanalization in ischemic stroke: insights into mechanisms, imaging, and therapeutic strategies.Frontiers in pharmacology · 2026Review
- Peroxiredoxins in central nervous system: implications for chronic pain and anaesthetic-induced neurotoxicity management.Redox biology · 2025Review
- Ischemic Postconditioning Regulates New Cell Death Mechanisms in Stroke: Disulfidptosis.Biomolecules · 2024Article
- Peroxiredoxin 1 inhibits streptozotocin-induced Alzheimer's disease-like pathology in hippocampal neuronal cells via the blocking of CaScientific reports · 2024Article
- Research hotspots and frontiers of preconditioning in cerebral ischemia: A bibliometric analysis.Heliyon · 2024Review
- Electroacupuncture ameliorates cerebrovascular impairment in Alzheimer's disease mice via melatonin signaling.CNS neuroscience & therapeutics · 2023Article
- The antioxidant enzyme Peroxiredoxin-1 controls stroke-associated microglia against acute ischemic stroke.Redox biology · 2022Article
- Peroxiredoxins wear many hats: Factors that fashion their peroxide sensing personalities.Redox biology · 2021Review
- Role of pericyte-derived SENP1 in neuronal injury after brain ischemia.CNS neuroscience & therapeutics · 2020Article
- Functional coupling of Tmem74 and HCN1 channels regulates anxiety-like behavior in BLA neurons.Molecular psychiatry · 2019Article
- Cathepsin B inhibition ameliorates leukocyte-endothelial adhesion in the BTBR mouse model of autism.CNS neuroscience & therapeutics · 2019Article
- GPR124 facilitates pericyte polarization and migration by regulating the formation of filopodia during ischemic injury.Theranostics · 2019Article
- Article
- Cholinergic Grb2-Associated-Binding Protein 1 Regulates Cognitive Function.Cerebral cortex (New York, N.Y. : 1991) · 2018Article
- Danger signals in stroke and their role on microglia activation after ischemia.Therapeutic advances in neurological disorders · 2018Review
- Melatonin ameliorates hypoglycemic stress-induced brain endothelial tight junction injury by inhibiting protein nitration of TP53-induced glycolysis and apoptosis regulator.Journal of pineal research · 2017Article
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 3 countries.
Funding
Abstract
aimsAlthough there is accumulating evidence that increased formation of reactive nitrogen species in cerebral vasculature contributes to the progression of ischemic damage, but the underlying molecular mechanisms remain elusive. Peroxiredoxin 1 (Prx1) can initiate the antioxidant response by scavenging free radicals. Therefore, we tested the hypothesis that Prx1 regulates the susceptibility to nitrosative stress damage during cerebral ischemia in vitro and in vivo.
resultsProteomic analysis in endothelial cells revealed that Prx1 was upregulated after stress-related oxygen-glucose deprivation (OGD). Although peroxynitrite upregulated Prx1 rapidly, this was followed by its polyubiquitination within 6 h after OGD mediated by the E3 ubiquitin ligase E6-associated protein (E6AP). OGD colocalized E6AP with nitrotyrosine in endothelial cells. To assess translational relevance in vivo, mice were studied after middle cerebral artery occlusion (MCAO). This was accompanied by Prx1 ubiquitination and degradation by the activation of E6AP. Furthermore, brain delivery of a lentiviral vector encoding Prx1 in mice inhibited blood-brain barrier leakage and neuronal damage significantly following MCAO. INNOVATION AND
conclusionsNitrosative stress during ischemic insult activates E6AP E3 ubiquitin ligase that ubiquitinates Prx1 and subsequently worsens cerebral damage. Thus, targeting the Prx1 antioxidant defense pathway may represent a novel treatment strategy for neurovascular protection in stroke.
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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.