Basal autophagy protects cardiomyocytes from doxorubicin-induced toxicity
Author
dc.contributor.author
Pizarro, Marcela
Author
dc.contributor.author
Troncoso Cotal, Rodrigo
Author
dc.contributor.author
Martínez, Gonzalo J.
Author
dc.contributor.author
Chiong Lay, Mario
Author
dc.contributor.author
Castro, Pablo F.
Author
dc.contributor.author
Lavandero González, Sergio
Admission date
dc.date.accessioned
2017-11-06T20:32:12Z
Available date
dc.date.available
2017-11-06T20:32:12Z
Publication date
dc.date.issued
2016
Cita de ítem
dc.identifier.citation
Toxicology 370 (2016) 41–48
es_ES
Identifier
dc.identifier.other
10.1016/j.tox.2016.09.011
Identifier
dc.identifier.uri
https://repositorio.uchile.cl/handle/2250/145486
Abstract
dc.description.abstract
Doxorubicin (Doxo) is one of the most effective anti-neoplastic agents but its cardiotoxicity has been an important clinical limitation. The major mechanism of Doxo-induced cardiotoxicity is associated to its oxidative capacity. However, other processes are also involved with significant consequences for the cardiomyocyte. In recent years, a number of studies have investigated the role of autophagy on Doxoinduced cardiotoxicity but to date it is not clear how Doxo alters that process and its consequence on cardiomyocytes viability. Here we investigated the effect of Doxo 1 uM for 24 h of stimulation on cultured neonatal rat cardiomyocytes. We showed that Doxo inhibits basal autophagy. This inhibition is due to both Akt/mTOR signaling pathway activation and Beclin 1 level decrease. To assess the role of autophagy on Doxo-induced cardiomyocyte death, we evaluated the effects 3-methyladenine (3-MA), bafilomycin A1 (BafA), siRNA Beclin 1 (siBeclin 1) and rapamycin (Rapa) on cell viability. Inhibition of autophagy with 3-MA, BafA and siBeclin 1 increased lactate dehydrogenase (LDH) release but, when autophagy was induced by Rapa, Doxo-induced cardiomyocyte death was decreased. These results suggest that Doxo inhibits basal autophagy and contributes to cardiomyocyte death. Activation of autophagy could be used as a strategy to protect the heart against Doxo toxicity.