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STAT1 Deficiency in the Heart Protects against Myocardial Infarction by Enhancing Autophagy.
MedLine Citation:
PMID:  21447043     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Previous studies have shown that the transcription factor Signal Transducer and Activator of Transcription 1 (STAT1) activation is increased in primary cardiac myocytes exposed to simulated ischaemia/reperfusion injury. This promotes apoptotic cell death by enhancing the expression of pro-apoptotic proteins. Autophagy has been demonstrated to play a cardioprotective role in the heart following myocardial infarction (MI). We therefore investigated the role of STAT1 in the intact heart subjected to MI and examined the contribution of autophagy in modulating the protective effect of STAT1 after MI injury. STAT1 deficient hearts had significantly smaller infarcts than wild type hearts and this correlated with increased levels of autophagy shown by LC3-I/LC3-II conversion, and up-regulation of Atg12 and Beclin 1. Moreover, pre-treatment with the autophagy inhibitor 3-MA reversed the cardioprotection observed in the STAT1 deficient hearts. These results reveal a new function of STAT1 in the control of autophagy and indicate a cross-talk between the cardioprotective versus the damaging effects of STAT1 in the intact heart exposed to MI injury.
Authors:
J McCormick; N Suleman; T M Scarabelli; R A Knight; D S Latchman; A Stephanou
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-3-29
Journal Detail:
Title:  Journal of cellular and molecular medicine     Volume:  -     ISSN:  1582-4934     ISO Abbreviation:  -     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-3-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101083777     Medline TA:  J Cell Mol Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
2011.
Affiliation:
Institute of Child Health, University College London, London, UK Wayne State University School of Medicine, USA.
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