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Cardioprotection mediated by urocortin is dependent on PKCepsilon activation

Cardioprotection mediated by urocortin is dependent on PKCepsilon activation
Cardioprotection mediated by urocortin is dependent on PKCepsilon activation
Urocortin (Ucn) is an endogenous cardioprotective agent that protects against the damaging effects of ischemia and reperfusion injury in vitro and in vivo. We have found that the mechanism of action of Ucn involves both acute activation of specific target molecules, and using Affymetrix (Santa Clara, CA) gene chip technology, altered gene expression of different end effector molecules. Here, from our gene chip data, we show that after a 24 h exposure to Ucn, there was a specific increase in mRNA and protein levels of the protein kinase C epsilon (PKC?) isozyme in primary rat cardiomyocytes compared with untreated cells and in the Langendorff perfused ex vivo heart. Furthermore, a short 10 min exposure of these cells to Ucn caused a specific translocation/activation of PKC? in vitro and in the Langendorff perfused ex vivo heart. The importance of the PKC? isozyme in cardioprotection and its relationship to cardioprotection produced by Ucn was assessed using PKC?-specific inhibitor peptides. The inhibitor peptide, when introduced into cardiomyocytes, caused an increase in apoptotic cell death compared with control peptide after ischemia and reperfusion. When the inhibitor peptide was present with Ucn, the cardioprotective effect of Ucn was lost. This loss of cardioprotection by Ucn was also seen in whole hearts from PKC? knockout mice. These findings indicate that the cardioprotective effect of Ucn is dependent upon PKC?.
ischemia, protein kinase c epsilon, apoptosis, mitochondria
0892-6638
831-833
Lawrence, Kevin M.
ff8347b7-930c-4414-beab-65f6d6514b73
Kabir, Alamgir M.N.
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Bellahcene, Mohammed
df3e5c28-eaaa-4331-ac97-756a9dee6f7e
Davidson, Sean
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Mesquita, Rue S.
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Cao, Xuebin
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McCormick, James
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Carroll, Christopher J.
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Chanalaris, Anastasios
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Townsend, Paul A.
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Hubank, Mike
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Stephanou, Anastasis
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Knight, Richard A.
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Marber, Michael S.
ff387cdb-b430-41f8-854f-15857b88d919
Latchman, David S.
71e9db7c-9075-4b49-afac-6413085378db
Lawrence, Kevin M.
ff8347b7-930c-4414-beab-65f6d6514b73
Kabir, Alamgir M.N.
7a7daa72-900e-486d-b6b8-5163ef85cb94
Bellahcene, Mohammed
df3e5c28-eaaa-4331-ac97-756a9dee6f7e
Davidson, Sean
8068199b-1568-42ac-a783-b4b90b6b59d0
Mesquita, Rue S.
c3c805a3-32ba-449a-8d1a-d7dd19b57193
Cao, Xuebin
f75452c7-f30c-4092-963d-f950a7823548
McCormick, James
9f5d47a6-87d4-48c3-a952-4133b710bbb1
Carroll, Christopher J.
83f87248-a322-4c00-b0e0-a54119376c26
Chanalaris, Anastasios
72d46901-69ac-4892-b713-4963b1b5d14f
Townsend, Paul A.
a2680443-664e-46d0-b4dd-97456ba810db
Hubank, Mike
ce4812f2-faca-42d9-ac80-7b5109698992
Stephanou, Anastasis
e9d502e8-693c-4458-a3c6-5e2844665db3
Knight, Richard A.
da6172f8-cacc-4330-871a-85dea9e893a4
Marber, Michael S.
ff387cdb-b430-41f8-854f-15857b88d919
Latchman, David S.
71e9db7c-9075-4b49-afac-6413085378db

Lawrence, Kevin M., Kabir, Alamgir M.N., Bellahcene, Mohammed, Davidson, Sean, Mesquita, Rue S., Cao, Xuebin, McCormick, James, Carroll, Christopher J., Chanalaris, Anastasios, Townsend, Paul A., Hubank, Mike, Stephanou, Anastasis, Knight, Richard A., Marber, Michael S. and Latchman, David S. (2005) Cardioprotection mediated by urocortin is dependent on PKCepsilon activation. The FASEB Journal, 19 (7), 831-833. (doi:10.1096/fj.04-2506fje).

Record type: Article

Abstract

Urocortin (Ucn) is an endogenous cardioprotective agent that protects against the damaging effects of ischemia and reperfusion injury in vitro and in vivo. We have found that the mechanism of action of Ucn involves both acute activation of specific target molecules, and using Affymetrix (Santa Clara, CA) gene chip technology, altered gene expression of different end effector molecules. Here, from our gene chip data, we show that after a 24 h exposure to Ucn, there was a specific increase in mRNA and protein levels of the protein kinase C epsilon (PKC?) isozyme in primary rat cardiomyocytes compared with untreated cells and in the Langendorff perfused ex vivo heart. Furthermore, a short 10 min exposure of these cells to Ucn caused a specific translocation/activation of PKC? in vitro and in the Langendorff perfused ex vivo heart. The importance of the PKC? isozyme in cardioprotection and its relationship to cardioprotection produced by Ucn was assessed using PKC?-specific inhibitor peptides. The inhibitor peptide, when introduced into cardiomyocytes, caused an increase in apoptotic cell death compared with control peptide after ischemia and reperfusion. When the inhibitor peptide was present with Ucn, the cardioprotective effect of Ucn was lost. This loss of cardioprotection by Ucn was also seen in whole hearts from PKC? knockout mice. These findings indicate that the cardioprotective effect of Ucn is dependent upon PKC?.

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More information

Published date: 2005
Keywords: ischemia, protein kinase c epsilon, apoptosis, mitochondria

Identifiers

Local EPrints ID: 24825
URI: http://eprints.soton.ac.uk/id/eprint/24825
ISSN: 0892-6638
PURE UUID: 531a77f9-a1c7-4f7a-a2a0-a5baa5e16485

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Date deposited: 03 Apr 2006
Last modified: 15 Mar 2024 06:58

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Contributors

Author: Kevin M. Lawrence
Author: Alamgir M.N. Kabir
Author: Mohammed Bellahcene
Author: Sean Davidson
Author: Rue S. Mesquita
Author: Xuebin Cao
Author: James McCormick
Author: Christopher J. Carroll
Author: Anastasios Chanalaris
Author: Paul A. Townsend
Author: Mike Hubank
Author: Anastasis Stephanou
Author: Richard A. Knight
Author: Michael S. Marber
Author: David S. Latchman

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