ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2001
p38 activation is required upstream of potassium current enhancement and caspase cleavage in thiol oxidant-induced neuronal apoptosis.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 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.
The trial behind it
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Who cites it
79 citing papers in PubMed, 172 citations in OpenAlex.
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- Metal Ion Signaling in Biomedicine.Chemical reviews · 2025Review
- Redox Regulation of KAntioxidants & redox signaling · 2024Review
- Modeling methamphetamine use disorder and relapse in animals: short- and long-term epigenetic, transcriptional., and biochemical consequences in the rat brain.Neuroscience and biobehavioral reviews · 2023Review
- Chemical Knockdown of Phosphorylated p38 Mitogen-Activated Protein Kinase (MAPK) as a Novel Approach for the Treatment of Alzheimer's Disease.ACS central science · 2023Article
- Zinc in Regulating Protein Kinases and Phosphatases in Neurodegenerative Diseases.Biomolecules · 2022Review
- Antagonistic roles of Ras-MAPK and Akt signaling in integrin-KFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- The Function and Regulation of Zinc in the Brain.Neuroscience · 2021Review
- Non-Cell-Autonomous Regulation of Optic Nerve Regeneration by Amacrine Cells.Frontiers in cellular neuroscience · 2021Review
- Targeted disruption of Kv2.1-VAPA association provides neuroprotection against ischemic stroke in mice by declustering Kv2.1 channels.Science advances · 2020Article
- ZnExperimental neurology · 2020Article
- Mechanism of Zinc Excitotoxicity: A Focus on AMPK.Frontiers in neuroscience · 2020Review
- The Redox Biology of Excitotoxic Processes: The NMDA Receptor, TOPA Quinone, and the Oxidative Liberation of Intracellular Zinc.Frontiers in neuroscience · 2020Review
- Mitochondrial ZnThe Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2019Article
- Molecular Neuroprotection Induced by Zinc-Dependent Expression of Hepatitis C-Derived Protein NS5A Targeting Kv2.1 Potassium Channels.The Journal of pharmacology and experimental therapeutics · 2018Article
- ZnExperimental neurology · 2018Article
- Impact of Labile Zinc on Heart Function: From Physiology to Pathophysiology.International journal of molecular sciences · 2017Review
- Disruption of KNeuroscience · 2017Article
- Targeting a Potassium Channel/Syntaxin Interaction Ameliorates Cell Death in Ischemic Stroke.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Zinc as a Neuromodulator in the Central Nervous System with a Focus on the Olfactory Bulb.Frontiers in cellular neuroscience · 2017Review
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Oxidant-induced neuronal apoptosis has been shown to involve potassium and zinc dysregulation, energetic dysfunction, activation of stress-related kinases, and caspase cleavage. The temporal ordering and interdependence of these events was investigated in primary neuronal cultures exposed to the sulfhydryl oxidizing agent 2,2'-dithiodipyridine (DTDP), a compound that induces the intracellular release of zinc. We previously observed that tetraethylammonium (TEA), high extracellular potassium, or cysteine protease inhibitors block apoptosis induced by DTDP. We now report that both p38 and extracellular signal-regulated kinase phosphorylation are evident in neuronal cultures within 2 hr of a brief exposure to 100 microm DTDP. However, only p38 inhibition is capable of blocking oxidant-induced toxicity. Cyclohexamide or actinomycin D does not attenuate DTDP-induced cell death, suggesting that posttranslational modification of existing targets, rather than transcriptional activation, is responsible for the deleterious effects of p38. Indeed, an early robust increase in TEA-sensitive potassium channel currents induced by DTDP is attenuated by p38 inhibition but not by caspase inhibition. Moreover, we found that activation of p38 is required for caspase 3 and 9 cleavage, suggesting that potassium currents enhancement is required for caspase activation. Finally, we observed that DTDP toxicity could be blocked with niacinamide or benzamide, inhibitors of poly (ADP-ribose) synthetase. Based on these findings, we conclude that oxidation of sulfhydryl groups on intracellular targets results in intracellular zinc release, p38 phosphorylation, enhancement of potassium currents, caspase cleavage, energetic dysfunction, and translationally independent apoptotic cell death.
Indexed as
Identifiers
11331359PMC3746747W1922083656What 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.