Oxidative Stress Stimulates Autophagic Flux During Ischemia/Reperfusion
Year: 2010
Type: article
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. H(2)O(2) 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.
Source: Antioxidants and Redox Signaling
Institution: Rutgers New Jersey Medical School
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
Awards: Regulation of myocardial growth and death by GSK-3, Longevity and Stress Resistance, Regulation of myocardial growth and death by autophagy, G4101633970, Redox regulation in myocardial disease, G4557971983, G5103921932, Myocardial Hypertrophy and Heart Failure, Intrinsic Vascular Smooth Muscle Cell Stiffness, Cardiovascular Control in Normal and Disease States, G7295199721, G7384925648, Mechanisms of myocardial ischemia and reperfusion, Cysteine oxidation in the heart
OpenAlex ID: W2026660662