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Effects of 3-methyladenine on isolated left atria subjected to simulated ischaemia-reperfusion.
MedLine Citation:
PMID:  25311855     Owner:  NLM     Status:  Publisher    
Although autophagy is a prominent feature of myocardial ischaemia and reperfusion, its functional significance is unclear and controversial. In order to gain a deeper insight into the role of autophagy in myocardial ischaemia-reperfusion, we explored the effects of the pharmacological inhibitor of autophagy 3-methyladenine (3-MA). Isolated rat atria subjected to simulated 75-minute ischaemia/75 minute-reperfusion (Is-Rs) in the presence or absence of 3-MA were used. The LC3-II/LC3-I ratio, an indicator of autophagosome formation, did not increase following ischaemia either in the presence or absence of 3-MA, but there was significant enhancement during reperfusion, which was prevented by the presence of 3-MA. The autophagy inhibitor also increased p62 protein, one of the specific substrates degraded through the autophagy-lysosomal pathway. Electron micrographs showed double membrane autophagosome-like structures during reperfusion, which were absent in atria subjected to Is-Rs in the presence of 3-MA. These findings suggest that this agent inhibited the autophagic flux under the present experimental conditions. Inhibition of autophagy during Is-Rs was accompanied by high incidence of tachyarrhythmias during reperfusion and a decrease in the maximal inotropic response to β-adrenergic and to calcium stimulation at the end of Is-Rs. Deterioration of mitochondrial morphology and function, without affecting cell viability, was observed in atria subjected to Is-Rs in the presence of 3-MA. The present results suggest an association between the inhibition of autophagy and functional alterations of the cells that have undergone sublethal stress and have been able to recover in this experimental model of ischaemia-reperfusion. This article is protected by copyright. All rights reserved.
Romina Hermann; Débora Elisabet Vélez; Tatiana Mariel Rusiecki; María de Las Mercedes Fernández Pazos; Victoria Evangelina Mestre Cordero; María Gabriela Marina Prendes; Juan Carlos Perazzo Rossini; Enrique Alberto Savino; Alicia Varela
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-10-14
Journal Detail:
Title:  Clinical and experimental pharmacology & physiology     Volume:  -     ISSN:  1440-1681     ISO Abbreviation:  Clin. Exp. Pharmacol. Physiol.     Publication Date:  2014 Oct 
Date Detail:
Created Date:  2014-10-14     Completed Date:  -     Revised Date:  2014-10-15    
Medline Journal Info:
Nlm Unique ID:  0425076     Medline TA:  Clin Exp Pharmacol Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
This article is protected by copyright. All rights reserved.
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