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Publication : P2X7 mediates superoxide production in primary microglia and is up-regulated in a transgenic mouse model of Alzheimer's disease.

First Author  Parvathenani LK Year  2003
Journal  J Biol Chem Volume  278
Issue  15 Pages  13309-17
PubMed ID  12551918 Mgi Jnum  J:82959
Mgi Id  MGI:2656136 Doi  10.1074/jbc.M209478200
Citation  Parvathenani LK, et al. (2003) P2X7 Mediates Superoxide Production in Primary Microglia and Is Up-regulated in a Transgenic Mouse Model of Alzheimer's Disease. J Biol Chem 278(15):13309-17
abstractText  Primary rat microglia stimulated with either ATP or 2'- and 3'-O-(4-benzoylbenzoyl)-ATP (BzATP) release copious amounts of superoxide (O(2)()). ATP and BzATP stimulate O(2)() production through purinergic receptors, primarily the P2X(7) receptor. O(2)() is produced through the activation of the NADPH oxidase. Although both p42/44 MAPK and p38 MAPK were activated rapidly in cells stimulated with BzATP, only pharmacological inhibition of p38 MAPK attenuated O(2)() production. Furthermore, an inhibitor of phosphatidylinositol 3-kinase attenuated O(2)() production to a greater extent than an inhibitor of p38 MAPK. Both ATP and BzATP stimulated microglia-induced cortical cell death indicating this pathway may contribute to neurodegeneration. Consistent with this hypothesis, P2X(7) receptor was specifically up-regulated around beta-amyloid plaques in a mouse model of Alzheimer's disease (Tg2576).
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