Document Detail


Arginylation regulates myofibrils to maintain heart function and prevent dilated cardiomyopathy.
MedLine Citation:
PMID:  22626847     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Protein arginylation mediated by arginyltransferase (ATE1) is essential for heart formation during embryogenesis, however its cell-autonomous role in cardiomyocytes and the differentiated heart muscle has never been investigated. To address this question, we generated cardiac muscle-specific Ate1 knockout mice, in which Ate1 deletion was driven by α-myosin heavy chain promoter (αMHC-Ate1 mouse). These mice were initially viable, but developed severe cardiac contractility defects, dilated cardiomyopathy, and thrombosis over time, resulting in high rates of lethality after 6months of age. These symptoms were accompanied by severe ultrastructural defects in cardiac myofibrils, seen in the newborns and far preceding the onset of cardiomyopathy, suggesting that these defects were primary and likely underlay the development of the future heart defects. Several major sarcomeric proteins were arginylated in vivo. Moreover, Ate1 deletion in the hearts resulted in a significant reduction of active and passive myofibril forces, suggesting that arginylation is critical for both myofibril structural integrity and contractility. Thus, arginylation is essential for maintaining the heart function by regulation of the major myofibril proteins and myofibril forces, and its absence in the heart muscle leads to progressive heart failure through cardiomyocyte-specific defects.
Authors:
Satoshi Kurosaka; N Adrian Leu; Ivan Pavlov; Xuemei Han; Paula Aver Bretanha Ribeiro; Tao Xu; Ralph Bunte; Sougata Saha; Junling Wang; Anabelle Cornachione; Wilfried Mai; John R Yates; Dilson E Rassier; Anna Kashina
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-05-21
Journal Detail:
Title:  Journal of molecular and cellular cardiology     Volume:  53     ISSN:  1095-8584     ISO Abbreviation:  J. Mol. Cell. Cardiol.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-08-13     Completed Date:  2012-12-17     Revised Date:  2013-09-03    
Medline Journal Info:
Nlm Unique ID:  0262322     Medline TA:  J Mol Cell Cardiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  333-41     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Ltd. All rights reserved.
Affiliation:
Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104, USA.
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MeSH Terms
Descriptor/Qualifier:
Aminoacyltransferases / genetics,  metabolism
Animals
Cardiomyopathy, Dilated / genetics,  metabolism*,  prevention & control
Genes, Lethal
Heart / physiology*
Mice
Mice, Knockout
Myocardial Contraction / genetics
Myocardium / metabolism,  ultrastructure
Myofibrils / metabolism*,  physiology
Sarcomeres / metabolism
Grant Support
ID/Acronym/Agency:
N01-HV-00243/HV/NHLBI NIH HHS; P41 RR011823/RR/NCRR NIH HHS; P41 RR011823/RR/NCRR NIH HHS; R01 HL084419/HL/NHLBI NIH HHS; R01 HL084419/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
EC 2.3.2.-/Aminoacyltransferases; EC 2.3.2.8/arginyltransferase
Comments/Corrections
Comment In:
J Mol Cell Cardiol. 2012 Sep;53(3):314-6   [PMID:  22749823 ]

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


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