ArticleThe Journal of biological chemistry2016
Dual Oxidase 2 (Duox2) Regulates Pannexin 1-mediated ATP Release in Primary Human Airway Epithelial Cells via Changes in Intracellular pH and Not H2O2 Production.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Pannexins in the vasculature.American journal of physiology. Heart and circulatory physiology · 2025Review
- Antigen stasis and airway nitrosative stress in human primary ciliary dyskinesia.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Activation of Pannexin-1 channels causes cell dysfunction and damage in mesangial cells derived from angiotensin II-exposed mice.Frontiers in cell and developmental biology · 2024Article
- Purinergic P2Y2 receptor-induced activation of endothelial TRPV4 channels mediates lung ischemia-reperfusion injury.Science signaling · 2023Article
- Hypertensive Nephropathy: Unveiling the Possible Involvement of Hemichannels and Pannexons.International journal of molecular sciences · 2022Review
- Purinergic receptors in airway hydration.Biochemical pharmacology · 2021Review
- SARS-CoV-2 early infection signature identified potential key infection mechanisms and drug targets.BMC genomics · 2021Article
- Consideration of Pannexin 1 channels in COVID-19 pathology and treatment.American journal of physiology. Lung cellular and molecular physiology · 2020Article
- Redox regulation of motile cilia in airway disease.Redox biology · 2019Review
- The Effects of the Anti-aging Protein Klotho on Mucociliary Clearance.Frontiers in medicine · 2019Article
- Genetic ablation of pannexin1 counteracts liver fibrosis in a chemical, but not in a surgical mouse model.Archives of toxicology · 2018Article
- Dual oxidase: a novel therapeutic target in allergic disease.British journal of pharmacology · 2018Review
- Carbenoxolone inhibits mechanical stress-induced osteogenic differentiation of mesenchymal stem cells by regulating p38 MAPK phosphorylation.Experimental and therapeutic medicine · 2018Article
- Klotho Inhibits Interleukin-8 Secretion from Cystic Fibrosis Airway Epithelia.Scientific reports · 2017Article
- Article
- Pannexin1 as mediator of inflammation and cell death.Biochimica et biophysica acta. Molecular cell research · 2017Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Human airway epithelial cells express pannexin 1 (Panx1) channels to release ATP, which regulates mucociliary clearance. Airway inflammation causes mucociliary dysfunction. Exposure of primary human airway epithelial cell cultures to IFN-γ for 48 h did not alter Panx1 protein expression but significantly decreased ATP release in response to hypotonic stress. The IFN-γ-induced functional down-regulation of Panx1 was due to the up-regulation of dual oxidase 2 (Duox2). Duox2 suppression by siRNA led to an increase in ATP release in control cells and restoration of ATP release in cells treated with IFN-γ. Both effects were reduced by the pannexin inhibitor probenecid. Duox2 up-regulation stoichiometrically increases H2O2 and proton production. H2O2 inhibited Panx1 function temporarily by formation of disulfide bonds at the thiol group of its terminal cysteine. Long-term exposure to H2O2, however, had no inhibitory effect. To assess the role of cellular acidification upon IFN-γ treatment, fully differentiated airway epithelial cells were exposed to ammonium chloride to alkalinize the cytosol. This led to a 2-fold increase in ATP release in cells treated with IFN-γ that was also inhibited by probenecid. Duox2 knockdown also partially corrected IFN-γ-mediated acidification. The direct correlation between intracellular pH and Panx1 open probability was shown in oocytes. Therefore, airway epithelial cells release less ATP in response to hypotonic stress in an inflammatory environment (IFN-γ exposure). Decreased Panx1 function is a response to cell acidification mediated by IFN-γ-induced up-regulation of Duox2, representing a novel mechanism for mucociliary dysfunction in inflammatory airway diseases.
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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.