RGD Reference Report - Oxidative stress stimulates autophagic flux during ischemia/reperfusion. - Rat Genome Database

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Oxidative stress stimulates autophagic flux during ischemia/reperfusion.

Authors: Hariharan, N  Zhai, P  Sadoshima, J 
Citation: Hariharan N, etal., Antioxid Redox Signal. 2011 Jun;14(11):2179-90. doi: 10.1089/ars.2010.3488. Epub 2011 Jan 27.
RGD ID: 11561944
Pubmed: PMID:20812860   (View Abstract at PubMed)
PMCID: PMC3085947   (View Article at PubMed Central)
DOI: DOI:10.1089/ars.2010.3488   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
BECN1HumanMyocardial Reperfusion Injury  ISOBecn1 (Mus musculus) RGD 
Becn1RatMyocardial Reperfusion Injury  ISOBecn1 (Mus musculus) RGD 
Becn1MouseMyocardial Reperfusion Injury  IMP  RGD 
MAP1LC3AHumanMyocardial Reperfusion Injury  ISOMap1lc3a (Mus musculus)protein:increased expression:heartRGD 
Map1lc3aRatMyocardial Reperfusion Injury  ISOMap1lc3a (Mus musculus)protein:increased expression:heartRGD 
Map1lc3aMouseMyocardial Reperfusion Injury  IEP protein:increased expression:heartRGD 

Objects Annotated

Genes (Rattus norvegicus)
Becn1  (beclin 1)
Map1lc3a  (microtubule-associated protein 1 light chain 3 alpha)

Genes (Mus musculus)
Becn1  (beclin 1, autophagy related)
Map1lc3a  (microtubule-associated protein 1 light chain 3 alpha)

Genes (Homo sapiens)
BECN1  (beclin 1)
MAP1LC3A  (microtubule associated protein 1 light chain 3 alpha)


Additional Information