| Lack of ATM induces structural and functional changes in the heart: Role in β-adrenergic receptor-stimulated apoptosis. | |
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MedLine Citation:
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PMID: 22179422 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Ataxia telangiectasia mutated kinase (ATM) is involved in cell cycle checkpoints, DNA repair and apoptosis. β-adrenergic receptor (β-AR) stimulation induces cardiac myocyte apoptosis. Here we analyzed basal myocardial structure and function in ATM knockout (KO) mice, and tested the hypothesis that ATM modulates β-AR-stimulated myocyte apoptosis. Left ventricular (LV) structure and function, myocyte apoptosis, fibrosis and expression of fibrosis-, hypertrophy- and apoptosis-related proteins were examined in wild-type (WT) and KO mice with or without L-isoproterenol treatment for 24h. Body and heart weights were lower in KO mice. M-mode echocardiography showed reduced septal wall thicknesses and LV diameters in KO mice. Doppler echocardiography showed increased ratio of early peak velocity (E wave) to that of the late (A wave) LV filling in KO mice. Basal fibrosis and myocyte cross-sectional area was greater in KO hearts. Expression of fibrosis-related genes (CTGF, PAI-1 and MMP-2) and hypertrophy-related gene (ANP) was higher in KO hearts. β-AR stimulation increased myocyte apoptosis to a similar extent in both groups. Activation of JNKs, and expression and phosphorylation of p53 in response to β-AR stimulation was only observed in WT group. Akt phosphorylation was lower in KO-sham and remained lower following β-AR stimulation in KO group. β-AR stimulation activated GSK-3β to a similar extent in both groups. Thus, lack of ATM induces structural and functional changes in the heart with enhanced myocardial fibrosis and myocyte hypertrophy. β-AR-stimulated apoptosis in WT hearts involves p53- and JNKs-dependent mechanism, while decreased Akt activity may play a role in increased myocyte apoptosis in the absence of ATM. |
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Authors:
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Cerrone R Foster; Qinqin Zha; Laura L Daniel; Mahipal Singh; Krishna Singh |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-16 |
Journal Detail:
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Title: Experimental physiology Volume: - ISSN: 1469-445X ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-19 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9002940 Medline TA: Exp Physiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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East Tennessee State University. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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