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Title
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Cyclic AMP-dependent down regulation of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) in rat C6 glioma
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Author
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Abstract
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| 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. |
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Language
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English
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Source (journal)
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European journal of pharmacology. - Amsterdam, 1967, currens
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Publication
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Amsterdam
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North-Holland
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2011
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ISSN
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0014-2999
[print]
1879-0712
[online]
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DOI
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10.1016/J.EJPHAR.2010.11.031
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Volume/pages
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654
:1
(2011)
, p. 1-9
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ISI
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000287291200001
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Full text (Publisher's DOI)
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