| http://purl.uniprot.org/citations/18703049 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18703049 | http://www.w3.org/2000/01/rdf-schema#comment | "We have previously shown that the beta-blocking drug metoprolol improves cardiac function in the streptozotocin-diabetic rat partly by inducing parallel improvements in cardiac metabolism and gene expression. beta-blockers have been previously reported to increase the expression of beta(1) and beta(2)-adrenoceptors, but their effects on the expression of beta(3)-adrenoceptors are unknown. The aim of the present study was to investigate whether metoprolol increases beta(3)-adrenoceptor expression and downstream Akt-mediated signaling. Left ventricular function was measured in paced isolated working hearts. beta(1), beta(2) and beta(3) adrenoceptor-expression levels were measured using Western blotting. Protein kinase A (PKA) and calcium/calmodulin dependent protein kinase II (CAMK-II) activities, as well as Akt phosphorylation, were measured as indices of downstream target activation. Chronic metoprolol treatment improved cardiac function and produced a marked increase in the expression of all three beta-adrenoceptor subtypes which was associated with a decrease in PKA activity and an increase in Akt phosphorylation. Akt-mediated phosphorylation of endothelial nitric oxide synthase (eNOS) was not altered, but phosphorylation of the transcription factor FOXO-3 was increased. Metoprolol increased the expression of beta(1), beta(2) and beta(3) adrenoceptors, associated with repression of FOXO-3 expression. beta-adrenoceptor signaling shifted from PKA to Akt-mediated signaling, associated with phosphorylation of FOXO-3 but not eNOS."xsd:string |
| http://purl.uniprot.org/citations/18703049 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.ejphar.2008.07.042"xsd:string |
| http://purl.uniprot.org/citations/18703049 | http://purl.uniprot.org/core/author | "Sharma V."xsd:string |
| http://purl.uniprot.org/citations/18703049 | http://purl.uniprot.org/core/author | "Parsons H."xsd:string |
| http://purl.uniprot.org/citations/18703049 | http://purl.uniprot.org/core/author | "McNeill J.H."xsd:string |
| http://purl.uniprot.org/citations/18703049 | http://purl.uniprot.org/core/author | "Allard M.F."xsd:string |
| http://purl.uniprot.org/citations/18703049 | http://purl.uniprot.org/core/date | "2008"xsd:gYear |
| http://purl.uniprot.org/citations/18703049 | http://purl.uniprot.org/core/name | "Eur J Pharmacol"xsd:string |
| http://purl.uniprot.org/citations/18703049 | http://purl.uniprot.org/core/pages | "44-51"xsd:string |
| http://purl.uniprot.org/citations/18703049 | http://purl.uniprot.org/core/title | "Metoprolol increases the expression of beta(3)-adrenoceptors in the diabetic heart: effects on nitric oxide signaling and forkhead transcription factor-3."xsd:string |
| http://purl.uniprot.org/citations/18703049 | http://purl.uniprot.org/core/volume | "595"xsd:string |
| http://purl.uniprot.org/citations/18703049 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/18703049 |
| http://purl.uniprot.org/citations/18703049 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/18703049 |
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| http://purl.uniprot.org/uniprot/#_A6IVX3-mappedCitation-18703049 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18703049 |
| http://purl.uniprot.org/uniprot/#_P26255-mappedCitation-18703049 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18703049 |
| http://purl.uniprot.org/uniprot/P26255 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/18703049 |
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