Role of Beclin 1-dependent Autophagy in Cardioprotection of Ischemic Preconditioning

Emerging evidence indicates that ischemic preconditioning (IPC) induces autophagy which attenuates myocardial ischemia/reperfusion (I/R) injury. However, the precise mechanisms remain com- plex and unclear. The present study was to investigate which autophagy pathway was involved in the cardioprotec...

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Published inJournal of Huazhong University of Science and Technology. Medical sciences Vol. 33; no. 1; pp. 51 - 56
Main Author 彭雯 刘艺 徐卫娟 夏清华
Format Journal Article
LanguageEnglish
Published Heidelberg Huazhong University of Science and Technology 01.02.2013
Department of Geriatrics,Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China%Department of Cardiac Surgery, Wuhan Asia Heart Hospital Wuhan 430022, China%Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
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Summary:Emerging evidence indicates that ischemic preconditioning (IPC) induces autophagy which attenuates myocardial ischemia/reperfusion (I/R) injury. However, the precise mechanisms remain com- plex and unclear. The present study was to investigate which autophagy pathway was involved in the cardioprotection induced by IPC, so that we can acquire an attractive treatment way for iscbemic heart disease. Adult male Sprague-Dawley (SD) rats were randomly divided into sham group, I/R group and IPC group. IPC was induced with three cycles of 5 min regional ischemia alternating with 5 m~n reper- fusion in a heart I/R model. Samples were taken from the center of the infracted heart and examined by using the electron microscopy, the terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) method, Western blotting and co-immunoprecipitation (Co-IP). A large number of autophagic vacuoles were observed in the cardiomyocytes oflPC group as compared with I/R group. LC3-II forma- tion, an autophagy marker, was up-regulated in IPC group as compared with FR group (P〈0.05). Moreover, the interaction between Beclin 1 and Bcl-2 was significantly increased in IPC group as com- pared with I/R group (P〈0.01). It was also found that IPC decreased I/R-induced apoptosis (P〈0.01). These results suggest that IPC inhibits Beclin 1-dependent excessive autophagy in reperfusion phase and cooperates with anti-apoptosis pathway to diminish the cell death induced by the myocardial I/R injury.
Bibliography:autophagy; acute myocardial ischemia-reperfusion injury; ischemic preconditioning; Beclin 1; Bcl-2
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Emerging evidence indicates that ischemic preconditioning (IPC) induces autophagy which attenuates myocardial ischemia/reperfusion (I/R) injury. However, the precise mechanisms remain com- plex and unclear. The present study was to investigate which autophagy pathway was involved in the cardioprotection induced by IPC, so that we can acquire an attractive treatment way for iscbemic heart disease. Adult male Sprague-Dawley (SD) rats were randomly divided into sham group, I/R group and IPC group. IPC was induced with three cycles of 5 min regional ischemia alternating with 5 m~n reper- fusion in a heart I/R model. Samples were taken from the center of the infracted heart and examined by using the electron microscopy, the terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) method, Western blotting and co-immunoprecipitation (Co-IP). A large number of autophagic vacuoles were observed in the cardiomyocytes oflPC group as compared with I/R group. LC3-II forma- tion, an autophagy marker, was up-regulated in IPC group as compared with FR group (P〈0.05). Moreover, the interaction between Beclin 1 and Bcl-2 was significantly increased in IPC group as com- pared with I/R group (P〈0.01). It was also found that IPC decreased I/R-induced apoptosis (P〈0.01). These results suggest that IPC inhibits Beclin 1-dependent excessive autophagy in reperfusion phase and cooperates with anti-apoptosis pathway to diminish the cell death induced by the myocardial I/R injury.
ObjectType-Article-1
SourceType-Scholarly Journals-1
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content type line 23
ISSN:1672-0733
1993-1352
DOI:10.1007/s11596-013-1070-6