title: STAT1 deficiency in the heart protects against myocardial infarction by enhancing autophagy.
abstract: 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 light chain 3 (LC3)-I/LC3-II conversion, and up-regulation of Atg12 and Beclin 1. Moreover, pre-treatment with the autophagy inhibitor 3-methyladenine 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: Institute of Child Health, University College London, London, UK.
authors: J
authors: J
authors: McCormick
authors: N
authors: N
authors: Suleman
authors: T M
authors: TM
authors: Scarabelli
authors: R A
authors: RA
authors: Knight
authors: D S
authors: DS
authors: Latchman
authors: A
authors: A
authors: Stephanou
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000235:genetics*; D000071192:Autophagy-Related Protein 12; D000071186:Beclin-1; D002316:Cardiotonic Agents; D006321:Heart; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009203:Myocardial Infarction / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism*; D011506:Proteins; D050794:STAT1 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C491971:Atg12 protein, mouse; D000071192:Autophagy-Related Protein 12; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D002316:Cardiotonic Agents; D008869:Microtubule-Associated Proteins; D011506:Proteins; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D016159:Tumor Suppressor Protein p53; C025946:3-methyladenine; D000225:Adenine