| ATP-P2X7 receptor signaling controls basal and TNFα-stimulated glial cell proliferation. | |
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MedLine Citation:
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PMID: 22298391 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Activation and proliferation of glial cells and their progenitors is a key process of neuroinflammation associated with many neurodegenerative disorders. Under neuropathological conditions where glial cell activation and proliferation is evident, controlling the population of glia might be of therapeutic importance. The proliferative action of the cytokine tumor necrosis factor alpha (TNFα) on microglia has been reported, but the molecular mechanism of TNFα regulation of glial cell proliferation is largely unknown. Using a model of organotypic hippocampal-entorhinal cortex (HEC) slice culture, we investigated the role of ATP-P2X(7) receptor signaling in glial proliferation by TNFα. Populations of proliferating cells in HEC culture were labeled with 5-bromo-2'-deoxyuridine (BrdU). Treatment with TNFα induced strong expression of P2X(7) receptor mRNA and immunoreactivity in BrdU+ cells while markedly increasing proliferation of BrdU+ cells. In addition, TNFα increased aquaporin 4 (AQP4) expression, an ion channel involved in glial proliferation. The proliferative action of TNFα was attenuated by blocking the P2X(7) receptors with the specific antagonists oxATP, BBG, and KN62, or by lowering extracellular ATP with ATP hydrolysis apyrase. Basal proliferation of BrdU+ cells was also sensitive to blockade of ATP-P2X(7) signaling. Furthermore, TNFα activation of P2X(7) receptors appear to regulate AQP4 expression through protein kinase C cascade and down regulation of AQP4 expression can reduce TNFα-stimulated BrdU+ cell proliferation. Taken together, these novel findings demonstrate the importance of ATP-P2X(7) signaling in controlling proliferation of glial progenitors under the pathological conditions associated with increased TNFα. |
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Authors:
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Jian Zou; Ryan P Vetreno; Fulton T Crews |
Publication Detail:
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Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-02-01 |
Journal Detail:
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Title: Glia Volume: 60 ISSN: 1098-1136 ISO Abbreviation: Glia Publication Date: 2012 Apr |
Date Detail:
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Created Date: 2012-02-09 Completed Date: 2012-06-12 Revised Date: 2013-05-20 |
Medline Journal Info:
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Nlm Unique ID: 8806785 Medline TA: Glia Country: United States |
Other Details:
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Languages: eng Pagination: 661-73 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 Wiley Periodicals, Inc. |
Affiliation:
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Bowles Center for Alcohol Studies, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7178, USA. jzou@med.unc.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Triphosphatases
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pharmacology Adenosine Triphosphate / analogs & derivatives, pharmacology Animals Animals, Newborn Aquaporin 4 / metabolism Bromodeoxyuridine / metabolism Calcium-Binding Proteins / metabolism Cell Proliferation / drug effects* Dose-Response Relationship, Drug Entorhinal Cortex / cytology Enzyme Inhibitors / pharmacology Gene Knockout Techniques Hippocampus / cytology Ivermectin / pharmacology Microfilament Proteins / metabolism Neuroglia / drug effects* Organ Culture Techniques Purinergic P2X Receptor Agonists / pharmacology Purinergic P2X Receptor Antagonists / pharmacology RNA, Small Interfering / metabolism Rats Rats, Sprague-Dawley Receptors, Purinergic P2X7 / metabolism* Signal Transduction / drug effects, physiology* Time Factors Tumor Necrosis Factor-alpha / pharmacology* |
| Grant Support | |
ID/Acronym/Agency:
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AA019767/AA/NIAAA NIH HHS; AA020022/AA/NIAAA NIH HHS; AA020023/AA/NIAAA NIH HHS; AA020024/AA/NIAAA NIH HHS; AA11605/AA/NIAAA NIH HHS; P60 AA011605-06/AA/NIAAA NIH HHS; U01 AA020023-01/AA/NIAAA NIH HHS; U24 AA020022-01/AA/NIAAA NIH HHS; U24 AA020024-01/AA/NIAAA NIH HHS; U54 AA019767-01/AA/NIAAA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Aif1 protein, rat; 0/Aqp4 protein, rat; 0/Aquaporin 4; 0/Calcium-Binding Proteins; 0/Enzyme Inhibitors; 0/Microfilament Proteins; 0/Purinergic P2X Receptor Agonists; 0/Purinergic P2X Receptor Antagonists; 0/RNA, Small Interfering; 0/Receptors, Purinergic P2X7; 0/Tumor Necrosis Factor-alpha; 56-65-5/Adenosine Triphosphate; 59-14-3/Bromodeoxyuridine; 70288-86-7/Ivermectin; 81790-82-1/3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; EC 3.6.1.-/Adenosine Triphosphatases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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