| Activation of the cardiac proteasome during pressure overload promotes ventricular hypertrophy. | |
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MedLine Citation:
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PMID: 17043166 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: The adaptation of cardiac mass to hemodynamic overload requires an adaptation of protein turnover, ie, the balance between protein synthesis and degradation. We tested 2 hypotheses: (1) chronic left ventricular hypertrophy (LVH) activates the proteasome system of protein degradation, especially in the myocardium submitted to the highest wall stress, ie, the subendocardium, and (2) the proteasome system is required for the development of LVH. METHODS AND RESULTS: Gene and protein expression of proteasome subunits and proteasome activity were measured separately from left ventricular subendocardium and subepicardium, right ventricle, and peripheral tissues in a canine model of severe, chronic (2 years) LVH induced by aortic banding and then were compared with controls. Both gene and protein expressions of proteasome subunits were increased in LVH versus control (P<0.05), which was accompanied by a significant (P<0.05) increase in proteasome activity. Posttranslational modification of the proteasome was also detected by 2-dimensional gel electrophoresis. These changes were found specifically in left ventricular subendocardium but not in left ventricular subepicardium, right ventricle, or noncardiac tissues from the same animals. In a mouse model of chronic pressure overload, a 50% increase in heart mass and a 2-fold increase in proteasome activity (both P<0.05 versus sham) were induced. In that model, the proteasome inhibitor epoxomicin completely prevented LVH while blocking proteasome activation. CONCLUSIONS: The increase in proteasome expression and activity found during chronic pressure overload in myocardium submitted to higher stress is also required for the establishment of LVH. |
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Authors:
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Christophe Depre; Qian Wang; Lin Yan; Nadia Hedhli; Pallavi Peter; Li Chen; Chull Hong; Luc Hittinger; Bijan Ghaleh; Junichi Sadoshima; Dorothy E Vatner; Stephen F Vatner; Kiran Madura |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2006-10-16 |
Journal Detail:
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Title: Circulation Volume: 114 ISSN: 1524-4539 ISO Abbreviation: Circulation Publication Date: 2006 Oct |
Date Detail:
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Created Date: 2006-10-24 Completed Date: 2006-11-08 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 0147763 Medline TA: Circulation Country: United States |
Other Details:
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Languages: eng Pagination: 1821-8 Citation Subset: AIM; IM |
Affiliation:
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Department of Cell Biology & Molecular Medicine, UMDNJ, Newark, NJ 07103, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adaptation, Physiological Animals Aorta, Thoracic Disease Models, Animal Dogs Electrophoresis, Gel, Two-Dimensional Female Gene Expression Profiling Hypertrophy, Left Ventricular / metabolism* Ligation Male Mice Muscle Proteins / metabolism* Myocytes, Cardiac / drug effects, enzymology, pathology Oligopeptides / pharmacology Polyubiquitin / metabolism Protease Inhibitors / pharmacology Proteasome Endopeptidase Complex / antagonists & inhibitors, physiology* Protein Subunits Stress, Physiological / metabolism Ventricular Remodeling / physiology* |
| Grant Support | |
ID/Acronym/Agency:
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AG023039/AG/NIA NIH HHS; AG028854/AG/NIA NIH HHS; AG14121/AG/NIA NIH HHS; AG23137/AG/NIA NIH HHS; CA83875/CA/NCI NIH HHS; HL067724/HL/NHLBI NIH HHS; HL069752/HL/NHLBI NIH HHS; HL33107/HL/NHLBI NIH HHS; HL59139/HL/NHLBI NIH HHS; HL65182/HL/NHLBI NIH HHS; HL65183/HL/NHLBI NIH HHS; HL69020/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Muscle Proteins; 0/Oligopeptides; 0/Protease Inhibitors; 0/Protein Subunits; 120904-94-1/Polyubiquitin; 134381-21-8/epoxomicin; EC 3.4.25.1/Proteasome Endopeptidase Complex |
| Comments/Corrections | |
Comment In:
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Circulation. 2006 Oct 24;114(17):1796-8
[PMID:
17060395
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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