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Cyclic AMP-dependent down regulation of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) in rat C6 glioma.

Authors: Aerts, Indra  Grobben, Bert  Van Ostade, Xaveer  Slegers, Herman 
Citation: Aerts I, etal., Eur J Pharmacol. 2011 Mar 1;654(1):1-9. doi: 10.1016/j.ejphar.2010.11.031. Epub 2010 Dec 16.
Pubmed: (View Article at PubMed) PMID:21168404
DOI: Full-text: DOI:10.1016/j.ejphar.2010.11.031

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 ß-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 48h of stimulation, 1mM dbcAMP or 5µM (-)-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 Ca(2+), 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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CRRD Object Information
CRRD ID: 13204723
Created: 2017-07-14
Species: All species
Last Modified: 2017-07-14
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.