| pubmed-article:16040722 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:16040722 | lifeskim:mentions | umls-concept:C0034785 | lld:lifeskim |
| pubmed-article:16040722 | lifeskim:mentions | umls-concept:C1280500 | lld:lifeskim |
| pubmed-article:16040722 | lifeskim:mentions | umls-concept:C0443199 | lld:lifeskim |
| pubmed-article:16040722 | lifeskim:mentions | umls-concept:C0449560 | lld:lifeskim |
| pubmed-article:16040722 | lifeskim:mentions | umls-concept:C0127400 | lld:lifeskim |
| pubmed-article:16040722 | pubmed:issue | 6 | lld:pubmed |
| pubmed-article:16040722 | pubmed:dateCreated | 2005-11-14 | lld:pubmed |
| pubmed-article:16040722 | pubmed:abstractText | Recent data suggest that beta-adrenergic receptor subtypes couple differentially to signaling pathways regulating cardiac function vs. cardiac remodeling. To dissect the roles of beta1- vs. beta2-receptors in the pathogenesis of cardiomyopathy, doxorubicin was administered to beta1, beta2, and beta1/beta2 knockout (-/-) and wild-type mice. Expression and activation of MAPKs were measured. Wild-type and beta1-/- mice showed no acute cardiovascular effects, whereas beta2-/- mice all died within 30 min. The additional deletion of the beta1-receptor (beta1/beta2-/-) totally rescued this toxicity. beta2-/- mice developed decreased contractile function, hypotension, QTc prolongation, and ST segment changes and a 20-fold increase in p38 MAPK activity not seen in the other genotypes. The MAPK inhibitor SB-203580 rescued beta2-/- mice from this acute toxicity. The enhanced toxicity in beta2-/- mice was also recapitulated in wild-type mice with the beta2-selective antagonist ICI-118,551, although the rescue effect of the beta1-deletion was not recapitulated using the beta1-selective antagonist metoprolol or the nonselective beta-antagonist propranolol. These data suggest that beta2-adrenergic receptors play a cardioprotective role in the pathogenesis of cardiomyopathy, whereas beta1-adrenergic receptors mediate at least some of the acute cardiotoxicity of anthracyclines. Differential activation of MAPK isoforms, previously shown in vitro to regulate beta-agonist as well as doxorubicin cardiotoxicity, appears to play a role in mediating the differential effects of these beta-adrenergic receptor subtypes in vivo. | lld:pubmed |
| pubmed-article:16040722 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16040722 | pubmed:language | eng | lld:pubmed |
| pubmed-article:16040722 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16040722 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:16040722 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16040722 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16040722 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16040722 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:16040722 | pubmed:month | Dec | lld:pubmed |
| pubmed-article:16040722 | pubmed:issn | 0363-6135 | lld:pubmed |
| pubmed-article:16040722 | pubmed:author | pubmed-author:KobilkaBrian... | lld:pubmed |
| pubmed-article:16040722 | pubmed:author | pubmed-author:ZhaoMingmingM | lld:pubmed |
| pubmed-article:16040722 | pubmed:author | pubmed-author:BernsteinDani... | lld:pubmed |
| pubmed-article:16040722 | pubmed:author | pubmed-author:UrashimaTakas... | lld:pubmed |
| pubmed-article:16040722 | pubmed:author | pubmed-author:BerryGeraldG | lld:pubmed |
| pubmed-article:16040722 | pubmed:author | pubmed-author:PowersJennife... | lld:pubmed |
| pubmed-article:16040722 | pubmed:author | pubmed-author:FajardoGiovan... | lld:pubmed |
| pubmed-article:16040722 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:16040722 | pubmed:volume | 289 | lld:pubmed |
| pubmed-article:16040722 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:16040722 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:16040722 | pubmed:pagination | H2441-9 | lld:pubmed |
| pubmed-article:16040722 | pubmed:dateRevised | 2007-11-14 | lld:pubmed |
| pubmed-article:16040722 | pubmed:meshHeading | pubmed-meshheading:16040722... | lld:pubmed |
| pubmed-article:16040722 | pubmed:meshHeading | pubmed-meshheading:16040722... | lld:pubmed |
| pubmed-article:16040722 | pubmed:meshHeading | pubmed-meshheading:16040722... | lld:pubmed |
| pubmed-article:16040722 | pubmed:meshHeading | pubmed-meshheading:16040722... | lld:pubmed |
| pubmed-article:16040722 | pubmed:meshHeading | pubmed-meshheading:16040722... | lld:pubmed |
| pubmed-article:16040722 | pubmed:meshHeading | pubmed-meshheading:16040722... | lld:pubmed |
| pubmed-article:16040722 | pubmed:meshHeading | pubmed-meshheading:16040722... | lld:pubmed |
| pubmed-article:16040722 | pubmed:meshHeading | pubmed-meshheading:16040722... | lld:pubmed |
| pubmed-article:16040722 | pubmed:meshHeading | pubmed-meshheading:16040722... | lld:pubmed |
| pubmed-article:16040722 | pubmed:meshHeading | pubmed-meshheading:16040722... | lld:pubmed |
| pubmed-article:16040722 | pubmed:year | 2005 | lld:pubmed |
| pubmed-article:16040722 | pubmed:articleTitle | Differential cardioprotective/cardiotoxic effects mediated by beta-adrenergic receptor subtypes. | lld:pubmed |
| pubmed-article:16040722 | pubmed:affiliation | Dept. of Pediatrics, 750 Welch Rd., Suite 305, Palo Alto, CA 94304, USA. danb@stanford.edu | lld:pubmed |
| pubmed-article:16040722 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:16040722 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| pubmed-article:16040722 | pubmed:publicationType | Research Support, N.I.H., Extramural | lld:pubmed |
| entrez-gene:11554 | entrezgene:pubmed | pubmed-article:16040722 | lld:entrezgene |
| entrez-gene:11555 | entrezgene:pubmed | pubmed-article:16040722 | lld:entrezgene |
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