ArticleAutophagy2015
A novel mechanism of autophagic cell death in dystrophic muscle regulated by P2RX7 receptor large-pore formation and HSP90.
Article in Autophagy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 81 citations in OpenAlex.
- Vitamin D alleviates intracerebral hemorrhage symptoms by modulating pro-inflammatory/anti-inflammatory phenotypic transformation of microglia through P2X7R activation of NLRP3.IBRO neuroscience reports · 2026Article
- Methodological guidelines for P2X receptor assays and data interpretation.Cell death & disease · 2026Review
- Cellular senescence in migraine - a hypothesis-driven narrative review.The journal of headache and pain · 2026Review
- Alleviation of nitroglycerin-induced migraine in rats: inhibition of central sensitization by optimizing Qinggan Jieyu decoction regulation of purinergic receptor P2X ligand-gated ion channel 7 and autophagy.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2026Article
- P2RX7 Dynamics in CNS Disorders: Molecular Insights and Therapeutic Perspectives.Molecular neurobiology · 2025Review
- Chloroquine decreases cardiac fibrosis and improves cardiac function in a mouse model of Duchenne muscular dystrophy.PloS one · 2024Article
- The Role of P2X7 Purinoceptors in the Pathogenesis and Treatment of Muscular Dystrophies.International journal of molecular sciences · 2023Review
- Specific Dystrophins Selectively Associate with Inhibitory and Excitatory Synapses of the Mouse Cerebellum and their Loss Alters Expression of P2X7 Purinoceptors and Pro-Inflammatory Mediators.Cellular and molecular neurobiology · 2022Article
- Article
- P2X7 Receptor Antagonist Reduces Fibrosis and Inflammation in a Mouse Model of Alpha-Sarcoglycan Muscular Dystrophy.Pharmaceuticals (Basel, Switzerland) · 2022Article
- P2X7 receptor isoform B is a key drug resistance mediator for neuroblastoma.Frontiers in oncology · 2022Article
- P2X7 Purinoceptor Affects Ectopic Calcification of Dystrophic Muscles.Frontiers in pharmacology · 2022Article
- Comparative Proteomic Analysis of the DiatomFrontiers in plant science · 2022Article
- Reciprocal interactions between gut microbiota and autophagy.World journal of gastroenterology · 2021Review
- To inhibit or to boost the ATP/P2RX7 pathway to fight cancer-that is the question.Purinergic signalling · 2021Review
- Moderate-intensity exercise alleviates pyroptosis by promoting autophagy in osteoarthritis via the P2X7/AMPK/mTOR axis.Cell death discovery · 2021Article
- Disrupted Calcium Homeostasis in Duchenne Muscular Dystrophy: A Common Mechanism behind Diverse Consequences.International journal of molecular sciences · 2021Review
- Novel P2X7 Antagonist Ameliorates the Early Phase of ALS Disease and Decreases Inflammation and Autophagy in SOD1-G93A Mouse Model.International journal of molecular sciences · 2021Article
- P2X7R-mediated autophagic impairment contributes to central sensitization in a chronic migraine model with recurrent nitroglycerin stimulation in mice.Journal of neuroinflammation · 2021Article
- The P2X7 Receptor in Osteoarthritis.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
P2RX7 is an ATP-gated ion channel, which can also exhibit an open state with a considerably wider permeation. However, the functional significance of the movement of molecules through the large pore (LP) and the intracellular signaling events involved are not known. Here, analyzing the consequences of P2RX7 activation in primary myoblasts and myotubes from the Dmd(mdx) mouse model of Duchenne muscular dystrophy, we found ATP-induced P2RX7-dependent autophagic flux, leading to CASP3-CASP7-independent cell death. P2RX7-evoked autophagy was triggered by LP formation but not Ca(2+) influx or MAPK1-MAPK3 phosphorylation, 2 canonical P2RX7-evoked signals. Phosphoproteomics, protein expression inference and signaling pathway prediction analysis of P2RX7 signaling mediators pointed to HSPA2 and HSP90 proteins. Indeed, specific HSP90 inhibitors prevented LP formation, LC3-II accumulation, and cell death in myoblasts and myotubes but not in macrophages. Pharmacological blockade or genetic ablation of p2rx7 also proved protective against ATP-induced death of muscle cells, as did inhibition of autophagy with 3-MA. The functional significance of the P2RX7 LP is one of the great unknowns of purinergic signaling. Our data demonstrate a novel outcome--autophagy--and show that molecules entering through the LP can be targeted to phagophores. Moreover, we show that in muscles but not in macrophages, autophagy is needed for the formation of this LP. Given that P2RX7-dependent LP and HSP90 are critically interacting in the ATP-evoked autophagic death of dystrophic muscles, treatments targeting this axis could be of therapeutic benefit in this debilitating and incurable form of muscular dystrophy.
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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.