Document Detail


Activation of the cardiac proteasome during pressure overload promotes ventricular hypertrophy.
MedLine Citation:
PMID:  17043166     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2006-10-16
Journal Detail:
Title:  Circulation     Volume:  114     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-10-24     Completed Date:  2006-11-08     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1821-8     Citation Subset:  AIM; IM    
Affiliation:
Department of Cell Biology & Molecular Medicine, UMDNJ, Newark, NJ 07103, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
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:
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:
Circulation. 2006 Oct 24;114(17):1796-8   [PMID:  17060395 ]

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