Document Detail


Decreased energetics in murine hearts bearing the R92Q mutation in cardiac troponin T.
MedLine Citation:
PMID:  12952925     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The thin filament protein cardiac troponin T (cTnT) is an important regulator of myofilament activation. Here we report a significant change in cardiac energetics in transgenic mice bearing the missense mutation R92Q within the tropomyosin-binding domain of cTnT, a mutation associated with a clinically severe form of familial hypertrophic cardiomyopathy. This functional domain of cTnT has recently been shown to be a crucial modulator of contractile function despite the fact that it does not directly interact with the ATP hydrolysis site in the myosin head. Simultaneous measurements of cardiac energetics using 31P NMR spectroscopy and contractile performance of the intact beating heart revealed both a decrease in the free energy of ATP hydrolysis available to support contractile work and a marked inability to increase contractile performance upon acute inotropic challenge in hearts from R92Q mice. These results show that alterations in thin filament protein structure and function can lead to significant defects in myocardial energetics and contractile reserve.
Authors:
Maryam M Javadpour; Jil C Tardiff; Ilka Pinz; Joanne S Ingwall
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  112     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2003 Sep 
Date Detail:
Created Date:  2003-09-03     Completed Date:  2003-09-25     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  768-75     Citation Subset:  AIM; IM    
Affiliation:
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / metabolism
Animals
Cardiomyopathy, Hypertrophic / genetics*
Disease Models, Animal
Energy Metabolism*
Humans
Mice
Mutation*
Myocardial Contraction
Myocardium / metabolism*
Troponin T / genetics*
Grant Support
ID/Acronym/Agency:
HL-53230/HL/NHLBI NIH HHS; K08 HL-68619/HL/NHLBI NIH HHS; R01-HL-63985/HL/NHLBI NIH HHS; T32 HL-10435/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Troponin T; 56-65-5/Adenosine Triphosphate
Comments/Corrections
Comment In:
J Clin Invest. 2003 Sep;112(5):652-4   [PMID:  12952912 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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