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). |