title: NO-induced activation of cyclic GMP-dependent pathway down regulates ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) protein in rat C6 glioma.
abstract: In rat C6 glioma cells, the ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (NPP1), a modulator of purinergic receptor signaling, is down regulated after an increase in intracellular cAMP by addition of dibutyryl cAMP, a membrane-permeable cAMP-analog, or by activation of the β-adrenoceptor receptor with (-)-isoproterenol (Aerts et al., 2011, Eur. J. Pharmacol. 654, 1-9). In this communication we studied the effect of nitric oxide (NO)/cGMP, a pathway also affecting purinergic receptor signaling, on the level of NPP1 protein. Sodium nitroprusside (SNP), a NO donor, reduces NPP1 protein in a dose-dependent manner. A combination of SNP and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, an inhibitor of soluble guanylate cyclase, demonstrated that NO-dependent down regulation of NPP1 was caused by NO-sensitive guanylyl cyclase. Treatment with Rp-pCPT-cGMPS, an inhibitor of protein kinase G (PKG), showed that PKG is not involved in the down regulation of NPP1. In addition, we have shown that the cAMP- and cGMP-dependent decrease in NPP1 expression is unrelated. These results indicate that NO/cGMP regulates the level of NPP1 protein by a pathway that differs from the cAMP-induced decrease in NPP1.
authors.affiliation: Department of Biomedical Science, Cellular Biochemistry, Campus Drie Eiken, University of Antwerp, Belgium.
authors.forename: Indra
authors.initials: I
authors.lastname: Aerts
authors.affiliation: Department of Biomedical Science, Laboratory Proteinscience, Proteomics and Epigenetic Signalling, Campus Drie Eiken, University of Antwerp, Belgium.
authors.forename: Xaveer
authors.initials: X
authors.lastname: Van Ostade
authors.affiliation: Department of Biomedical Science, Cellular Biochemistry, Campus Drie Eiken, University of Antwerp, Belgium.
authors.forename: Herman
authors.initials: H
authors.lastname: Slegers
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects*; D005910:Glioma / Q000473:pathology*; D006162:Guanylate Cyclase / Q000737:chemistry / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D011755:Pyrophosphatases / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D012995:Solubility
chemical_list: D009569:Nitric Oxide; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases; D006162:Guanylate Cyclase; D006152:Cyclic GMP