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Mechanisms of P2X7 receptor-mediated ERK1/2 phosphorylation in human astrocytoma cells

Mechanisms of P2X7 receptor-mediated ERK1/2 phosphorylation in human astrocytoma cells Abstract Astrocytes are involved in normal and pathological brain functions, where they become activated and undergo reactive gliosis. Astrocytes have been shown to respond to extracellular nucleotides via the activation of P2 receptors, either G protein-coupled P2Y receptors or P2X receptors that are ligand-gated ion channels. In this study, we have examined the manner in which activation of the P2X 7 nucleotide receptor, an extracellular ATP-gated ion channel expressed in astrocytes, can lead to the phosphorylation of ERK1/2. Results showed that the P2X 7 receptor agonist 2′,3′- O -(4-benzoyl)benzoyl-ATP induced ERK1/2 phosphorylation in human astrocytoma cells overexpressing the recombinant rat P2X 7 receptor (rP2X 7 -R), a response that was inhibited by the P2X 7 receptor antagonist, oxidized ATP. Other results suggest that rP2X 7 -R-mediated ERK1/2 phosphorylation was linked to the phosphorylation of the proline-rich/Ca 2+ -activated tyrosine kinase Pyk2, c-Src, phosphatidylinositol 3′-kinase, and protein kinase Cδ activities and was dependent on the presence of extracellular Ca 2+ . These results support the hypothesis that the P2X 7 receptor and its signaling pathways play a role in astrocyte-mediated inflammation and neurodegenerative disease. astrocytes P2 nucleotide receptors ligand-gated ion channels protein kinase C mitogen-activated protein kinases Footnotes Present address of P. M. Theiss: Virginia Mason Research Center, Benaroya Research Institute, 1201 Ninth Ave., Seattle, WA 98101-2795. Address for reprint requests and other correspondence: F. P. Gendron, Dept. of Biochemistry, Univ. of Missouri-Columbia, M121 Medical Sciences Bldg., Columbia, MO 65212 (E-mail: gendronf@health.missouri.edu or fpgendron@hotmail.com ). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 10.1152/ajpcell.00286.2002 Copyright © 2003 the American Physiological Society http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Cell Physiology The American Physiological Society

Mechanisms of P2X7 receptor-mediated ERK1/2 phosphorylation in human astrocytoma cells

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References (60)

Publisher
The American Physiological Society
Copyright
Copyright © 2010 the American Physiological Society
ISSN
0363-6143
eISSN
1522-1563
DOI
10.1152/ajpcell.00286.2002
pmid
12529254
Publisher site
See Article on Publisher Site

Abstract

Abstract Astrocytes are involved in normal and pathological brain functions, where they become activated and undergo reactive gliosis. Astrocytes have been shown to respond to extracellular nucleotides via the activation of P2 receptors, either G protein-coupled P2Y receptors or P2X receptors that are ligand-gated ion channels. In this study, we have examined the manner in which activation of the P2X 7 nucleotide receptor, an extracellular ATP-gated ion channel expressed in astrocytes, can lead to the phosphorylation of ERK1/2. Results showed that the P2X 7 receptor agonist 2′,3′- O -(4-benzoyl)benzoyl-ATP induced ERK1/2 phosphorylation in human astrocytoma cells overexpressing the recombinant rat P2X 7 receptor (rP2X 7 -R), a response that was inhibited by the P2X 7 receptor antagonist, oxidized ATP. Other results suggest that rP2X 7 -R-mediated ERK1/2 phosphorylation was linked to the phosphorylation of the proline-rich/Ca 2+ -activated tyrosine kinase Pyk2, c-Src, phosphatidylinositol 3′-kinase, and protein kinase Cδ activities and was dependent on the presence of extracellular Ca 2+ . These results support the hypothesis that the P2X 7 receptor and its signaling pathways play a role in astrocyte-mediated inflammation and neurodegenerative disease. astrocytes P2 nucleotide receptors ligand-gated ion channels protein kinase C mitogen-activated protein kinases Footnotes Present address of P. M. Theiss: Virginia Mason Research Center, Benaroya Research Institute, 1201 Ninth Ave., Seattle, WA 98101-2795. Address for reprint requests and other correspondence: F. P. Gendron, Dept. of Biochemistry, Univ. of Missouri-Columbia, M121 Medical Sciences Bldg., Columbia, MO 65212 (E-mail: gendronf@health.missouri.edu or fpgendron@hotmail.com ). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 10.1152/ajpcell.00286.2002 Copyright © 2003 the American Physiological Society

Journal

AJP - Cell PhysiologyThe American Physiological Society

Published: Feb 1, 2003

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