P2X(7)/P2Z purinoreceptor-mediated activation of transcription factor NFATin microglial cells

Citation
D. Ferrari et al., P2X(7)/P2Z purinoreceptor-mediated activation of transcription factor NFATin microglial cells, J BIOL CHEM, 274(19), 1999, pp. 13205-13210
Citations number
51
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
00219258 → ACNP
Volume
274
Issue
19
Year of publication
1999
Pages
13205 - 13210
Database
ISI
SICI code
0021-9258(19990507)274:19<13205:PPAOTF>2.0.ZU;2-3
Abstract
ATP is released from neurons and other cell types during several physiologi cal and stress conditions under which it exerts various biological effects upon binding to purinoreceptors, A rather peculiar purinoreceptor called P2 X(7)/P2Z is expressed on microglial and other myeloic cells. Although incre asing evidence implicates an important role for P2Z in inflammatory process es, little information exists about underlying signaling pathways. Here, we report that in N9 microglial cells, extracellular ATP potently activates n uclear factor of activated T cells (NFAT), a central transcription factor i nvolved in cytokine gene expression. ATP activated NFAT rapidly (within 1 m in), whereas activation of nuclear factor kappa B was much delayed, with st rikingly distinct kinetics, During ATP stimulation, both NFAT-1 and NFAT-2 were activated by a calcineurin dependent pathway that required the influx of extracellular calcium ions. Based on the pharmacological profile, NFAT a ctivation was specifically mediated by P2Z and not by other purinoreceptors . Ne cells that lacked P2Z but still expressed P2Y purinoreceptors failed t o respond to NFAT activation. We conclude that P2Z-mediated NFAT activation may represent a novel mechanism by which extracellular ATP can modulate ea rly inflammatory gene expression within the nervous and immune system.