ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2004
Peroxynitrite-induced neuronal apoptosis is mediated by intracellular zinc release and 12-lipoxygenase activation.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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Who cites it
90 citing papers in PubMed, 191 citations in OpenAlex.
- Allosteric activation of Trx1 by antagonizing nitrative modification at tyrosine 49 confers neuroprotection against ischemic stroke.Redox biology · 2026Article
- Zinc dyshomeostasis, mitochondrial dysfunction, and their pathological cycle in ischemic stroke pathophysiology: Mechanisms and potential therapeutic targets.Redox biology · 2026Review
- The zinc-nitric oxide axis in acute brain injury: Convergent oxidative-nitrative stress, peroxynitrite signaling, and therapeutic targets.Redox biology · 2026Review
- Nanomolar Cadmium Disrupts Neurotransmitter Release Timing via a ROS-dependent Mechanism at the Mouse Neuromuscular Junction: Modulation by Nanomolar ZnNeurochemical research · 2026Article
- The role of ALOX15 in inflammation-related diseases.Frontiers in immunology · 2026Review
- Glutamate gradually elevates [ZnScientific reports · 2025Article
- Natural flavonoids from herbs and nutraceuticals as ferroptosis inhibitors in central nervous system diseases: current preclinical evidence and future perspectives.Frontiers in pharmacology · 2025Review
- Mechanism of ferroptosis regulating ischemic stroke and pharmacologically inhibiting ferroptosis in treatment of ischemic stroke.CNS neuroscience & therapeutics · 2024Review
- Targeted RNAseq Revealed the Gene Expression Signature of Ferroptosis-Related Processes Associated with Disease Severity in Patients with Multiple Sclerosis.International journal of molecular sciences · 2024Article
- Cochlear zinc signaling dysregulation is associated with noise-induced hearing loss, and zinc chelation enhances cochlear recovery.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Synthesis of Zinc Oxide-Doped Carbon Dots for Treatment of Triple-Negative Breast Cancer.International journal of nanomedicine · 2024Article
- Pathophysiological Roles of Transient Receptor Potential (Trp) Channels and Zinc Toxicity in Brain Disease.International journal of molecular sciences · 2023Review
- Brain fatty acid and transcriptome profiles of pig fed diets with different levels of soybean oil.BMC genomics · 2023Article
- Non-conducting functions of potassium channels in cancer and neurological disease.Current topics in membranes · 2023Review
- Postoperative Delirium in Neurosurgical Patients: Recent Insights into the Pathogenesis.Brain sciences · 2022Review
- Potential Utility of Natural Products against Oxidative Stress in Animal Models of Multiple Sclerosis.Antioxidants (Basel, Switzerland) · 2022Review
- The ZIP3 Zinc Transporter Is Localized to Mossy Fiber Terminals and Is Required for Kainate-Induced Degeneration of CA3 Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Vitamin E Exerts Neuroprotective Effects in Pentylenetetrazole Kindling Epilepsy via Suppression of Ferroptosis.Neurochemical research · 2022Article
- 12/15-Lipoxygenase debilitates mitochondrial health in intermittent hypobaric hypoxia induced neuronal damage: An in vivo study.Redox biology · 2022Article
- The Function and Regulation of Zinc in the Brain.Neuroscience · 2021Review
30 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Peroxynitrite toxicity is a major cause of neuronal injury in stroke and neurodegenerative disorders. The mechanisms underlying the neurotoxicity induced by peroxynitrite are still unclear. In this study, we observed that TPEN [N,N,N',N'-tetrakis (2-pyridylmethyl)ethylenediamine], a zinc chelator, protected against neurotoxicity induced by exogenous as well as endogenous (coadministration of NMDA and a nitric oxide donor, diethylenetriamine NONOate) peroxynitrite. Two different approaches to detecting intracellular zinc release demonstrated the liberation of zinc from intracellular stores by peroxynitrite. In addition, we found that peroxynitrite toxicity was blocked by inhibitors of 12-lipoxygenase (12-LOX), p38 mitogen-activated protein kinase (MAPK), and caspase-3 and was associated with mitochondrial membrane depolarization. Inhibition of 12-LOX blocked the activation of p38 MAPK and caspase-3. Zinc itself induced the activation of 12-LOX, generation of reactive oxygen species (ROS), and activation of p38 MAPK and caspase-3. These data suggest a cell death pathway triggered by peroxynitrite in which intracellular zinc release leads to activation of 12-LOX, ROS accumulation, p38 activation, and caspase-3 activation. Therefore, therapies aimed at maintaining intracellular zinc homeostasis or blocking activation of 12-LOX may provide a novel avenue for the treatment of inflammation, stroke, and neurodegenerative diseases in which the formation of peroxynitrite is thought to be one of the important causes of cell death.
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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.