Oxidative Stress Stimulates Autophagic Flux During Ischemia/Reperfusion
Publication: Antioxidants & Redox Signaling
Volume 14, Issue Number 11
Abstract
Autophagy is a bulk degradation process in which cytosolic proteins and organelles are degraded through lysosomes. To evaluate autophagic flux in cardiac myocytes, we generated adenovirus and cardiac-specific transgenic mice harboring tandem fluorescent mRFP-GFP-LC3. Starvation significantly increased the number of mRFP-GFP-LC3 dots representing both autophagosomes and autolysosomes per cell, suggesting that autophagic flux is increased in cardiac myocytes. H2O2 significantly increased autophagic flux, which was attenuated in the presence of N-2-mercaptopropionyl glycine (MPG), an antioxidant, suggesting that oxidative stress stimulates autophagy in cardiac myocytes. Myocardial ischemia/reperfusion (I/R) increased both autophagosomes and autolysosomes, thereby increasing autophagic flux. Treatment with MPG attenuated I/R-induced increases in oxidative stress, autophagic flux, and Beclin-1 expression, accompanied by a decrease in the size of myocardial infarction (MI)/area at risk (AAR), suggesting that oxidative stress plays an important role in mediating autophagy and myocardial injury during I/R. MI/AAR after I/R was significantly reduced in beclin1+/− mice, whereas beclin1+/− mice treated with MPG exhibited no additional reduction in the size of MI/AAR after I/R. These results suggest that oxidative stress plays an important role in mediating autophagy during I/R, and that activation of autophagy through oxidative stress mediates myocardial injury in response to I/R in the mouse heart. Antioxid. Redox Signal. 14, 2179–2190.
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Information & Authors
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Published In
Antioxidants & Redox Signaling
Volume 14 • Issue Number 11 • June 2011
Pages: 2179 - 2190
PubMed: 20812860
Copyright
Copyright 2011, Mary Ann Liebert, Inc.
History
Published in print: June 2011
Published online: 12 May 2011
Published ahead of print: 27 January 2011
Published ahead of production: 2 September 2010
Accepted: 2 September 2010
Received: 16 August 2010
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No competing financial interests exist.
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