Urocortin inhibits Beclin1-mediated autophagic cell death in cardiac myocytes exposed to ischaemia/reperfusion injury
Urocortin inhibits Beclin1-mediated autophagic cell death in cardiac myocytes exposed to ischaemia/reperfusion injury
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.
cardiac, research, myocytes, injuries, apoptosis, rats, adult, animals, cytology, inhibition, london, proteins, cardiomyopathies, survival, autophagy, autophagocytosis
846-852
Valentim, Lauren
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Laurence, Kevin M.
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Townsend, Paul A.
a2680443-664e-46d0-b4dd-97456ba810db
Carroll, Christopher J.
83f87248-a322-4c00-b0e0-a54119376c26
Soond, Surinder
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Scarabelli, Tiziano M.
ac96a777-880e-4e39-9884-f11a0978da35
Knight, Richard A.
da6172f8-cacc-4330-871a-85dea9e893a4
Latchman, David S.
71e9db7c-9075-4b49-afac-6413085378db
Stephanou, Anastasis
e9d502e8-693c-4458-a3c6-5e2844665db3
June 2006
Valentim, Lauren
f3d4c760-2f82-4ea7-98d9-738cd599adb5
Laurence, Kevin M.
b1dd3491-ef1b-4c2e-9c50-418b11d75948
Townsend, Paul A.
a2680443-664e-46d0-b4dd-97456ba810db
Carroll, Christopher J.
83f87248-a322-4c00-b0e0-a54119376c26
Soond, Surinder
02e8857e-b048-4080-8fe6-4c040c9b26b1
Scarabelli, Tiziano M.
ac96a777-880e-4e39-9884-f11a0978da35
Knight, Richard A.
da6172f8-cacc-4330-871a-85dea9e893a4
Latchman, David S.
71e9db7c-9075-4b49-afac-6413085378db
Stephanou, Anastasis
e9d502e8-693c-4458-a3c6-5e2844665db3
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), .
(doi:10.1016/j.yjmcc.2006.03.428).
Abstract
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.
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Published date: June 2006
Keywords:
cardiac, research, myocytes, injuries, apoptosis, rats, adult, animals, cytology, inhibition, london, proteins, cardiomyopathies, survival, autophagy, autophagocytosis
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Local EPrints ID: 60351
URI: http://eprints.soton.ac.uk/id/eprint/60351
PURE UUID: 61c25282-a077-4c52-82af-8f77616a71d5
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Date deposited: 08 Sep 2008
Last modified: 15 Mar 2024 11:20
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Contributors
Author:
Lauren Valentim
Author:
Kevin M. Laurence
Author:
Paul A. Townsend
Author:
Christopher J. Carroll
Author:
Surinder Soond
Author:
Tiziano M. Scarabelli
Author:
Richard A. Knight
Author:
David S. Latchman
Author:
Anastasis Stephanou
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