Oxidative stress stimulates autophagic flux during ischemia/reperfusion

Nirmala Hariharan, Peiyong Zhai, Junichi Sadoshima

Research output: Contribution to journalArticle

200 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2179-2190
Number of pages12
JournalAntioxidants and Redox Signaling
Volume14
Issue number11
DOIs
StatePublished - Jun 1 2011
Externally publishedYes

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Oxidative stress
Autophagy
Reperfusion
Oxidative Stress
Ischemia
Fluxes
Cardiac Myocytes
Glycine
Myocardial Infarction
Myocardial Reperfusion
Wounds and Injuries
Starvation
Lysosomes
Adenoviridae
Organelles
Transgenic Mice
Myocardial Ischemia
Antioxidants
Chemical activation
Degradation

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Physiology
  • Clinical Biochemistry

Cite this

Oxidative stress stimulates autophagic flux during ischemia/reperfusion. / Hariharan, Nirmala; Zhai, Peiyong; Sadoshima, Junichi.

In: Antioxidants and Redox Signaling, Vol. 14, No. 11, 01.06.2011, p. 2179-2190.

Research output: Contribution to journalArticle

Hariharan, Nirmala ; Zhai, Peiyong ; Sadoshima, Junichi. / Oxidative stress stimulates autophagic flux during ischemia/reperfusion. In: Antioxidants and Redox Signaling. 2011 ; Vol. 14, No. 11. pp. 2179-2190.
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