STAT1 deficiency in the heart protects against myocardial infarction by enhancing autophagy

被引：121

作者：

McCormick, J. ^{[1
]}

Suleman, N. ^{[1
]}

Scarabelli, T. M. ^{[2
]}

Knight, R. A. ^{[1
]}

Latchman, D. S. ^{[1
]}

Stephanou, A. ^{[1
]}

机构：

[1] UCL, Inst Child Hlth, London, England

[2] Wayne State Univ, Sch Med, Detroit, MI USA

来源：

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE | 2012年 / 16卷 / 02期

关键词：

STAT1; autophagy; cardioprotection; ischaemia; ISCHEMIA/REPERFUSION INJURY; ENDOTHELIAL-CELLS; APOPTOSIS; P53; REPERFUSION; ACTIVATION; MECHANISMS; PATHWAYS; ISCHEMIA; STRESS;

D O I：

10.1111/j.1582-4934.2011.01323.x

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

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.

引用

页码：386 / 393

页数：8

共 31 条

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IFN-γ-Inducible Irga6 Mediates Host Resistance against Chlamydia trachomatis via Autophagy [J].