ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2002
Ionic mechanism of ouabain-induced concurrent apoptosis and necrosis in individual cultured cortical neurons.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 1 of them a synthesis that pooled it.
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Who cites it
82 citing papers in PubMed, 1 synthesis or guideline pooled it, 241 citations in OpenAlex.
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- Extrasynaptic NMDA receptors in acute and chronic excitotoxicity: implications for preventive treatments of ischemic stroke and late-onset Alzheimer's disease.Molecular neurodegeneration · 2023Review
- Consequences of the Lack of TNFR1 in Ouabain Response in the Hippocampus of C57BL/6J Mice.Biomedicines · 2022Article
- Effects of In Vivo Intracellular ATP Modulation on Neocortical Extracellular Potassium Concentration.Biomedicines · 2022Article
- Monovalent ions and stress-induced senescence in human mesenchymal endometrial stem/stromal cells.Scientific reports · 2022Article
- Role of NaJournal of molecular medicine (Berlin, Germany) · 2022Review
- Pathogenesis of sporadic Alzheimer's disease by deficiency of NMDA receptor subunit GluN3A.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2022Article
- Pan-cerebral sodium elevations in vascular dementia: Evidence for disturbed brain-sodium homeostasis.Frontiers in aging neuroscience · 2022Article
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- Cinobufagin Is a Selective Anti-Cancer Agent against Tumors with EGFR Amplification and PTEN Deletion.Frontiers in pharmacology · 2021Article
- Deep Mutational Scan of anCirculation. Genomic and precision medicine · 2020Article
- Inflammasome inhibition blocks cardiac glycoside cell toxicity.The Journal of biological chemistry · 2019Article
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- Nicotine Effects on White Matter Microstructure in Young Adults.Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists · 2019Article
- DR-region of NaCell death & disease · 2018Article
- Mitochondrial respiratory chain inhibition and NaInterdisciplinary toxicology · 2018Article
- Energy handling in renal tubular epithelial cells of the hamster, a native hibernator, under warm anoxia or reoxygenation.Biomedical reports · 2018Article
- Article
22 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Energy deficiency and dysfunction of the Na+, K+-ATPase are common consequences of many pathological insults. The nature and mechanism of cell injury induced by impaired Na+, K+-ATPase, however, are not well defined. We used cultured cortical neurons to examine the hypothesis that blocking the Na+, K+-ATPase induces apoptosis by depleting cellular K+ and, concurrently, induces necrotic injury in the same cells by increasing intracellular Ca2+ and Na+. The Na+, K+-ATPase inhibitor ouabain induced concentration-dependent neuronal death. Ouabain triggered transient neuronal cell swelling followed by cell shrinkage, accompanied by intracellular Ca2+ and Na+ increase, K+ decrease, cytochrome c release, caspase-3 activation, and DNA laddering. Electron microscopy revealed the coexistence of ultrastructural features of both apoptosis and necrosis in individual cells. The caspase inhibitor Z-Val-Ala-Asp(OMe)-fluoromethyl ketone (Z-VAD-FMK) blocked >50% of ouabain-induced neuronal death. Potassium channel blockers or high K+ medium, but not Ca2+ channel blockade, prevented cytochrome c release, caspase activation, and DNA damage. Blocking of K+, Ca2+, or Na+ channels or high K+ medium each attenuated the ouabain-induced cell death; combined inhibition of K+ channels and Ca2+ or Na+ channels resulted in additional protection. Moreover, coapplication of Z-VAD-FMK and nifedipine produced virtually complete neuroprotection. These results suggest that the neuronal death associated with Na+, K+-pump failure consists of concurrent apoptotic and necrotic components, mediated by intracellular depletion of K+ and accumulation of Ca2+ and Na+, respectively. The ouabain-induced hybrid death may represent a distinct form of cell death related to the brain injury of inadequate energy supply and disrupted ion homeostasis.
Indexed as
Identifiers
11850462PMC6757565W1684019827What 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.