Document Detail


ATP-P2X7 receptor signaling controls basal and TNFα-stimulated glial cell proliferation.
MedLine Citation:
PMID:  22298391     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Jian Zou; Ryan P Vetreno; Fulton T Crews
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-02-01
Journal Detail:
Title:  Glia     Volume:  60     ISSN:  1098-1136     ISO Abbreviation:  Glia     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-02-09     Completed Date:  2012-06-12     Revised Date:  2014-09-24    
Medline Journal Info:
Nlm Unique ID:  8806785     Medline TA:  Glia     Country:  United States    
Other Details:
Languages:  eng     Pagination:  661-73     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Wiley Periodicals, Inc.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphatases / 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:
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/AA/NIAAA NIH HHS; P60 AA011605-06/AA/NIAAA NIH HHS; U01 AA020023/AA/NIAAA NIH HHS; U01 AA020023-01/AA/NIAAA NIH HHS; U24 AA020022/AA/NIAAA NIH HHS; U24 AA020022-01/AA/NIAAA NIH HHS; U24 AA020024/AA/NIAAA NIH HHS; U24 AA020024-01/AA/NIAAA NIH HHS; U54 AA019767/AA/NIAAA NIH HHS; U54 AA019767-01/AA/NIAAA NIH HHS
Chemical
Reg. No./Substance:
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; 70288-86-7/Ivermectin; 81790-82-1/3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; 8L70Q75FXE/Adenosine Triphosphate; EC 3.6.1.-/Adenosine Triphosphatases; G34N38R2N1/Bromodeoxyuridine
Comments/Corrections

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