ArticlePurinergic signalling2005
P2X(7) nucleotide receptors mediate caspase-8/9/3-dependent apoptosis in rat primary cortical neurons.
Article in Purinergic signalling, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 63 citations in OpenAlex.
- P2X7 receptor: A receptor closely linked with sepsis-associated encephalopathy.Open life sciences · 2024Review
- Recombinant Analogs of Sea Anemone Kunitz-Type Peptides Influence P2X7 Receptor Activity in Neuro-2a Cells.Marine drugs · 2023Article
- Nucleotide receptors mediate protection against neonatal sepsis and meningitis caused by alpha-hemolysin expressing Escherichia coli K1.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Article
- Role of Pannexin-1-P2X7R signaling on cell death and pro-inflammatory mediator expression induced byFrontiers in immunology · 2022Article
- Review
- Proteome profiling of different rat brain regions reveals the modulatory effect of prolonged maternal separation on proteins involved in cell death-related processes.Biological research · 2021Article
- Calcium-Handling Defects and Neurodegenerative Disease.Cold Spring Harbor perspectives in biology · 2020Review
- P2X7 Receptor is Involved in Mitochondrial Dysfunction Induced by Extracellular Alpha Synuclein in Neuroblastoma SH-SY5Y Cells.International journal of molecular sciences · 2020Article
- P2X7 Receptor-Dependent microRNA Expression Profile in the Brain Following Status Epilepticus in Mice.Frontiers in molecular neuroscience · 2020Article
- Evolutionary Origin of the P2X7 C-ter Region: Capture of an Ancient Ballast Domain by a P2X4-Like Gene in Ancient Jawed Vertebrates.Frontiers in immunology · 2020Article
- Positive allosteric modulation of P2X7 promotes apoptotic cell death over lytic cell death responses in macrophages.Cell death & disease · 2019Article
- Pleiotropic Roles of P2X7 in the Central Nervous System.Frontiers in cellular neuroscience · 2019Review
- P2RX7 Purinoceptor as a Therapeutic Target-The Second Coming?Frontiers in chemistry · 2018Review
- POM-1 inhibits P2 receptors and exhibits anti-inflammatory effects in macrophages.Purinergic signalling · 2017Article
- Purinergic Antagonism Prevents Mitochondrial Dysfunction and Behavioral Deficits Associated with Dopaminergic Toxicity Induced by 6-OHDA in Rats.Neurochemical research · 2017Article
- The Role of the P2X7 Receptor in Ocular Stresses: A Potential Therapeutic Target.Vision (Basel, Switzerland) · 2017Review
- Extracellular ATP protects pancreatic duct epithelial cells from alcohol-induced damage through P2Y1 receptor-cAMP signal pathway.Cell biology and toxicology · 2016Article
- Purinergic receptors as potential therapeutic targets in Alzheimer's disease.Neuropharmacology · 2016Review
- Silencing P2X7 receptor downregulates the expression of TCP-1 involved in lymphoma lymphatic metastasis.Oncotarget · 2015Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Apoptosis is a major cause of cell death in the nervous system. It plays a role in embryonic and early postnatal brain development and contributes to the pathology of neurodegenerative diseases. Here, we report that activation of the P2X(7) nucleotide receptor (P2X(7)R) in rat primary cortical neurons (rPCNs) causes biochemical (i.e., caspase activation) and morphological (i.e., nuclear condensation and DNA fragmentation) changes characteristic of apoptotic cell death. Caspase-3 activation and DNA fragmentation in rPCNs induced by the P2X(7)R agonist BzATP were inhibited by the P2X(7)R antagonist oxidized ATP (oATP) or by pre-treatment of cells with P2X(7)R antisense oligonucleotide indicating a direct involvement of the P2X(7)R in nucleotide-induced neuronal cell death. Moreover, Z-DEVD-FMK, a specific and irreversible cell permeable inhibitor of caspase-3, prevented BzATP-induced apoptosis in rPCNs. In addition, a specific caspase-8 inhibitor, Ac-IETD-CHO, significantly attenuated BzATP-induced caspase-9 and caspase-3 activation, suggesting that P2X(7)R-mediated apoptosis in rPCNs occurs primarily through an intrinsic caspase-8/9/3 activation pathway. BzATP also induced the activation of C-jun N-terminal kinase 1 (JNK1) and extracellular signal-regulated kinases (ERK1/2) in rPCNs, and pharmacological inhibition of either JNK1 or ERK1/2 significantly reduced caspase activation by BzATP. Taken together, these data indicate that extracellular nucleotides mediate neuronal apoptosis through activation of P2X(7)Rs and their downstream signaling pathways involving JNK1, ERK and caspases 8/9/3.
Identifiers
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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.