Linked Life Data

17068291

Source:http://linkedlifedata.com/resource/pubmed/id/17068291

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2006-11-23
pubmed:abstractText
Chronic stimulation of the beta-adrenergic neurohormonal axis contributes to the progression of heart failure and mortality in animal models and human patients. In cardiomyocytes, activation of the beta-adrenergic pathway has been shown to result in transiently increased expression of a cardiac small heat-shock protein Hsp20. The present study shows that cardiac overexpression (10-fold) of Hsp20 may protect the heart against beta-agonist-induced cardiac remodeling, associated with isoproterenol (50 mug/g per day) infusion for 14 days. Hsp20 attenuated the cardiac hypertrophic response, markedly reduced interstitial fibrosis, and decreased apoptosis. Contractility was also preserved in hearts with increased Hsp20 levels. These beneficial effects were associated with attenuation of the ASK1-JNK/p38 (apoptosis signal-regulating kinase 1/c-Jun NH(2)-terminal kinase/p38) signaling cascade triggered by isoproterenol, whereas there was no difference in either extracellular signal-related kinase 1/2 or Akt activation. Parallel in vitro experiments supported the inhibitory role of Hsp20 on enforced ASK1-JNK/p38 activation in both H9c2 cells and adult rat cardiomyocytes. Immunostaining studies also demonstrated that Hsp20 colocalizes with ASK1 in cardiomyocytes. Taken together, our findings indicate that (1) beta-agonist-induced cardiac injury is associated with activation of the ASK1-JNK/p38 cascade; (2) increased expression of Hsp20 attenuates the induction of remodeling, dysfunction, and apoptosis in response to sustained beta-adrenergic stimulation; and (3) the beneficial effects of Hsp20 are at least partially attributable to inhibition of the ASK1-signaling cascade.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
24
pubmed:volume
99
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1233-42
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17068291-Adrenergic beta-Agonists, pubmed-meshheading:17068291-Animals, pubmed-meshheading:17068291-Apoptosis, pubmed-meshheading:17068291-Cardiomegaly, pubmed-meshheading:17068291-Cardiotonic Agents, pubmed-meshheading:17068291-Cells, Cultured, pubmed-meshheading:17068291-Down-Regulation, pubmed-meshheading:17068291-Enzyme Activation, pubmed-meshheading:17068291-Fibrosis, pubmed-meshheading:17068291-HSP20 Heat-Shock Proteins, pubmed-meshheading:17068291-Heart, pubmed-meshheading:17068291-Isoproterenol, pubmed-meshheading:17068291-JNK Mitogen-Activated Protein Kinases, pubmed-meshheading:17068291-MAP Kinase Kinase Kinase 5, pubmed-meshheading:17068291-MAP Kinase Signaling System, pubmed-meshheading:17068291-Male, pubmed-meshheading:17068291-Mice, pubmed-meshheading:17068291-Mice, Transgenic, pubmed-meshheading:17068291-Myocardium, pubmed-meshheading:17068291-Myocytes, Cardiac, pubmed-meshheading:17068291-Phosphotransferases, pubmed-meshheading:17068291-Rats, pubmed-meshheading:17068291-Rats, Sprague-Dawley, pubmed-meshheading:17068291-Stress, Physiological, pubmed-meshheading:17068291-Ventricular Remodeling, pubmed-meshheading:17068291-p38 Mitogen-Activated Protein Kinases
pubmed:year
2006
pubmed:articleTitle
Small heat-shock protein Hsp20 attenuates beta-agonist-mediated cardiac remodeling through apoptosis signal-regulating kinase 1.
pubmed:affiliation
Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Ohio 45267-0575, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural