| http://purl.uniprot.org/citations/18456728 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18456728 | http://www.w3.org/2000/01/rdf-schema#comment | "ADP-ribosyl cyclase (ADPR-cyclase) produces a Ca(2+)-mobilizing second messenger, cADP-ribose (cADPR), from NAD(+). In this study, we investigated the molecular basis of ADPR-cyclase activation in the ANG II signaling pathway and cellular responses in adult rat cardiomyocytes. The results showed that ANG II generated biphasic intracellular Ca(2+) concentration increases that include a rapid transient Ca(2+) elevation via inositol trisphosphate (IP(3)) receptor and sustained Ca(2+) rise via the activation of L-type Ca(2+) channel and opening of ryanodine receptor. ANG II-induced sustained Ca(2+) rise was blocked by a cADPR antagonistic analog, 8-bromo-cADPR, indicating that sustained Ca(2+) rise is mediated by cADPR. Supporting the notion, ADPR-cyclase activity and cADPR production by ANG II were increased in a time-dependent manner. Application of pharmacological inhibitors and immunological analyses revealed that cADPR formation was activated by sequential activation of Src, phosphatidylinositol 3-kinase (PI 3-kinase)/protein kinase B (Akt), phospholipase C (PLC)-gamma1, and IP(3)-mediated Ca(2+) signal. Inhibitors of these signaling molecules not only completely abolished the ANG II-induced Ca(2+) signals but also inhibited cADPR formation. Application of the cADPR antagonist and inhibitors of upstream signaling molecules of ADPR-cyclase inhibited ANG II-stimulated hypertrophic responses, which include nuclear translocation of Ca(2+)/calcineurin-dependent nuclear factor of activated T cells 3, protein expression of transforming growth factor-beta1, and incorporation of [(3)H]leucine in cardiomyocytes. Taken together, these findings suggest that activation of ADPR-cyclase by ANG II entails a novel signaling pathway involving sequential activation of Src, PI 3-kinase/Akt, and PLC-gamma1/IP(3) and that the activation of ADPR-cyclase can lead to cardiac hypertrophy."xsd:string |
| http://purl.uniprot.org/citations/18456728 | http://purl.org/dc/terms/identifier | "doi:10.1152/ajpheart.01355.2007"xsd:string |
| http://purl.uniprot.org/citations/18456728 | http://purl.uniprot.org/core/author | "Kim S.J."xsd:string |
| http://purl.uniprot.org/citations/18456728 | http://purl.uniprot.org/core/author | "Kim S.Y."xsd:string |
| http://purl.uniprot.org/citations/18456728 | http://purl.uniprot.org/core/author | "Park K.H."xsd:string |
| http://purl.uniprot.org/citations/18456728 | http://purl.uniprot.org/core/author | "Kim B.J."xsd:string |
| http://purl.uniprot.org/citations/18456728 | http://purl.uniprot.org/core/author | "Kim U.H."xsd:string |
| http://purl.uniprot.org/citations/18456728 | http://purl.uniprot.org/core/author | "Im M.J."xsd:string |
| http://purl.uniprot.org/citations/18456728 | http://purl.uniprot.org/core/author | "Gul R."xsd:string |
| http://purl.uniprot.org/citations/18456728 | http://purl.uniprot.org/core/date | "2008"xsd:gYear |
| http://purl.uniprot.org/citations/18456728 | http://purl.uniprot.org/core/name | "Am J Physiol Heart Circ Physiol"xsd:string |
| http://purl.uniprot.org/citations/18456728 | http://purl.uniprot.org/core/pages | "H77-88"xsd:string |
| http://purl.uniprot.org/citations/18456728 | http://purl.uniprot.org/core/title | "A novel signaling pathway of ADP-ribosyl cyclase activation by angiotensin II in adult rat cardiomyocytes."xsd:string |
| http://purl.uniprot.org/citations/18456728 | http://purl.uniprot.org/core/volume | "295"xsd:string |
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