Urocortin inhibits Beclin1-mediated autophagic cell death in cardiac myocytes exposed to ischaemia/reperfusion injury
Valentim, Lauren, Laurence, Kevin M., Townsend, Paul A., Carroll, Christopher J., Soond, Surinder, Scarabelli, Tiziano M., Knight, Richard A., Latchman, David S. and Stephanou, Anastasis (2006) Urocortin inhibits Beclin1-mediated autophagic cell death in cardiac myocytes exposed to ischaemia/reperfusion injury. Journal of Molecular and Cellular Cardiology, 40, (6), 846-852. (doi:10.1016/j.yjmcc.2006.03.428).
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Autophagy is known to be a feature of cardiomyopathies and chronic ischaemia. Here we demonstrate that autophagy is also induced by a single cycle of ischaemia/reperfusion (I/R in neonatal and adult rat cardiac myocytes). Consistent with the critical role for Beclin1 in autophagocytosis, reduction of Beclin1 expression in cardiac myocytes by RNAi reduces I/R-induced autophagy and this is associated with enhanced cell survival. Autophagy is also reduced by urocortin, an endogenous cardiac peptide which we have previously shown to reduce other forms of myocyte cell death induced by I/R. The inhibition of autophagy by urocortin is mediated in part by inhibition of Beclin1 expression, an effect which is mediated by activation of the PI3 kinase/Akt pathway but which does not involve activation of p42/p44 MAPK.
|Keywords:||cardiac, research, myocytes, injuries, apoptosis, rats, adult, animals, cytology, inhibition, animals, london, proteins, cardiomyopathies, survival, autophagy, autophagocytosis|
|Subjects:||R Medicine > RD Surgery
R Medicine > RJ Pediatrics
|Divisions:||University Structure - Pre August 2011 > School of Medicine > Infection, Inflammation and Repair
University Structure - Pre August 2011 > School of Medicine
University Structure - Pre August 2011 > School of Medicine > Human Genetics
|Date Deposited:||08 Sep 2008|
|Last Modified:||01 Jun 2011 02:44|
|Contributors:||Valentim, Lauren (Author)
Laurence, Kevin M. (Author)
Townsend, Paul A. (Author)
Carroll, Christopher J. (Author)
Soond, Surinder (Author)
Scarabelli, Tiziano M. (Author)
Knight, Richard A. (Author)
Latchman, David S. (Author)
Stephanou, Anastasis (Author)
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