Title
Cyclic AMP-dependent down regulation of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) in rat C6 glioma Cyclic AMP-dependent down regulation of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) in rat C6 glioma
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Publication type
article
Publication
Amsterdam ,
Subject
Pharmacology. Therapy
Source (journal)
European journal of pharmacology. - Amsterdam
Volume/pages
654(2011) :1 , p. 1-9
ISSN
0014-2999
ISI
000287291200001
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
In this communication, we demonstrate that an increase in intracellular cAMP by 1) addition of dibutyrylic cAMP (dbcAMP), a membrane-permeable cAMP-analogue, or 2) activation of the β-adrenoceptor with (−)-isoproterenol, down regulates the levels of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) mRNA, NPP1 protein and ecto-NPPase activity in rat C6 glioma cells. DbcAMP and (−)-isoproterenol inhibit NPP1 expression in a time and dose-dependent manner. After 48 h of stimulation, 1 mM dbcAMP or 5 μM (−)-isoproterenol decreases the amount of NPP1 protein by 75 ± 3% and 81 ± 1% respectively. Contrary to down regulation of NPP1, we observe an up regulation of glial fibrillary acidic protein (GFAP), a differentiation marker for astrocytic cells. Using specific inhibitors and activators, we have shown that Ca2+, PKA, PI 3-K/PKB/GSK-3, Epac/Rap1/PP2A and MAP kinase modules are not involved in the inhibition of NPP1 gene expression. The transcription factor c-jun is significantly reduced while c-fos becomes up regulated after cAMP elevation. However an electrophoretic mobility shift assay with the activator protein-1 motif present in the promoter of the rat NPP1 gene indicates that this motif is not involved in the cAMP-dependent inhibition of NPP1 expression. In conclusion, these results indicate that intracellular cAMP levels regulate the expression of NPP1 in rat C6 glioma cells by a signalling pathway that is different from the GFAP signal transduction pathway.
E-info
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