Document Detail

Inhibition of Cap-initiation complexes linked to a novel mechanism of eIF4G depletion in acute myocardial ischemia.
MedLine Citation:
PMID:  16439989     Owner:  NLM     Status:  MEDLINE    
Translational control in the rat heart was characterized during acute myocardial ischemia introduced by left coronary artery ligature. Within 10 min of ischemia, eukaryotic (eIF)4E binds to its negative regulator, eIF4E-binding protein-1 (4E-BP1), but the levels of 4E-BP1 are insufficient to disrupt cap-dependent mRNA initiation complexes. However, by 1 h of ischemia, the abundance of the cap-initiation complex protein eIF4G is reduced by relocalization into TIAR protein complexes, triggering 4E-BP1 sequestration of eIF4E and disruption of cap-dependent mRNA initiation complexes. As the heart begins to fail at 6 h, proteolysis of eIF4G is observed, resulting in its depletion and accompanied by limited destruction of 4E-BP1 and eIF4E. eIF4G proteolysis and modest loss of 4E-BP1 are associated with caspase-3 activation and induction of cardiomyocyte apoptotic and necrotic death. Acute heart ischemia therefore downregulates cap-dependent translation through eIF4E sequestration triggered by eIF4G depletion.
E P Connolly; V Thuillier; D Rouy; G Bouétard; R J Schneider
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2006-01-27
Journal Detail:
Title:  Cell death and differentiation     Volume:  13     ISSN:  1350-9047     ISO Abbreviation:  Cell Death Differ.     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-08-14     Completed Date:  2006-11-21     Revised Date:  2014-02-21    
Medline Journal Info:
Nlm Unique ID:  9437445     Medline TA:  Cell Death Differ     Country:  England    
Other Details:
Languages:  eng     Pagination:  1586-94     Citation Subset:  IM    
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MeSH Terms
Acute Disease
Carrier Proteins / metabolism*
Caspase 3 / metabolism
Eukaryotic Initiation Factor-4E / metabolism*
Eukaryotic Initiation Factor-4G / metabolism*
Myocardial Ischemia / metabolism*,  pathology
Myocardium / metabolism*,  pathology
Myocytes, Cardiac / metabolism,  pathology
Phosphoproteins / metabolism*
RNA Caps
RNA, Messenger / metabolism
Rats, Sprague-Dawley
Transcription, Genetic
Grant Support
Reg. No./Substance:
0/Carrier Proteins; 0/Eif4ebp1 protein, rat; 0/Eukaryotic Initiation Factor-4E; 0/Eukaryotic Initiation Factor-4G; 0/Phosphoproteins; 0/RNA Caps; 0/RNA, Messenger; EC 3.4.22.-/Caspase 3

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

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