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The cardioprotective effect of urocortin during ischaemia/reperfusion involves the prevention of mitochondrial damage

The cardioprotective effect of urocortin during ischaemia/reperfusion involves the prevention of mitochondrial damage
The cardioprotective effect of urocortin during ischaemia/reperfusion involves the prevention of mitochondrial damage
We have previously shown, using Affymetrix gene chip technology, that urocortin induces the expression of several diverse genes in cardiac myocytes. An ATP sensitive inwardly rectifying potassium channel, Katp (Kir6.1), the enzyme calcium independent phospholipase A2 (iPLA2), and protein kinase C epsilon (PKC?) and that these genes are involved in the cardioprotective mechanism of action of urocortin. Here we demonstrate that these gene products are localized to cardiac myocyte mitochondria and for the first time show that urocortin protects cardiac myocytes from ischaemia/reperfusion induced cell death by preventing mitochondrial damage. Using pharmacological agents to Katp channels and iPLA2 and synthetic peptide inhibitors of PKC?, we go on to demonstrate that these three gene products are involved in the urocortin induced protection of cardiac myocyte mitochondria. These proteins may interact at the mitochondria to produce the protective effect.
urocortin, cardioprotection, mitochondria, katp channel, ipla2, pkc?
0006-291X
479-486
Lawrence, Kevin M.
ff8347b7-930c-4414-beab-65f6d6514b73
Townsend, Paul A.
a2680443-664e-46d0-b4dd-97456ba810db
Davidson, Sean M.
b8eeed87-5d86-42ca-8844-25bf6887253c
Carroll, Christopher J.
83f87248-a322-4c00-b0e0-a54119376c26
Eaton, Simon
e14103c2-c06a-45e6-87fe-2358a3371283
Hubank, Mike
ce4812f2-faca-42d9-ac80-7b5109698992
Knight, Richard A.
da6172f8-cacc-4330-871a-85dea9e893a4
Stephanou, Anastasis
e9d502e8-693c-4458-a3c6-5e2844665db3
Latchman, David S.
71e9db7c-9075-4b49-afac-6413085378db
Lawrence, Kevin M.
ff8347b7-930c-4414-beab-65f6d6514b73
Townsend, Paul A.
a2680443-664e-46d0-b4dd-97456ba810db
Davidson, Sean M.
b8eeed87-5d86-42ca-8844-25bf6887253c
Carroll, Christopher J.
83f87248-a322-4c00-b0e0-a54119376c26
Eaton, Simon
e14103c2-c06a-45e6-87fe-2358a3371283
Hubank, Mike
ce4812f2-faca-42d9-ac80-7b5109698992
Knight, Richard A.
da6172f8-cacc-4330-871a-85dea9e893a4
Stephanou, Anastasis
e9d502e8-693c-4458-a3c6-5e2844665db3
Latchman, David S.
71e9db7c-9075-4b49-afac-6413085378db

Lawrence, Kevin M., Townsend, Paul A., Davidson, Sean M., Carroll, Christopher J., Eaton, Simon, Hubank, Mike, Knight, Richard A., Stephanou, Anastasis and Latchman, David S. (2004) The cardioprotective effect of urocortin during ischaemia/reperfusion involves the prevention of mitochondrial damage. Biochemical and Biophysical Research Communications, 321 (2), 479-486. (doi:10.1016/j.bbrc.2004.06.170).

Record type: Article

Abstract

We have previously shown, using Affymetrix gene chip technology, that urocortin induces the expression of several diverse genes in cardiac myocytes. An ATP sensitive inwardly rectifying potassium channel, Katp (Kir6.1), the enzyme calcium independent phospholipase A2 (iPLA2), and protein kinase C epsilon (PKC?) and that these genes are involved in the cardioprotective mechanism of action of urocortin. Here we demonstrate that these gene products are localized to cardiac myocyte mitochondria and for the first time show that urocortin protects cardiac myocytes from ischaemia/reperfusion induced cell death by preventing mitochondrial damage. Using pharmacological agents to Katp channels and iPLA2 and synthetic peptide inhibitors of PKC?, we go on to demonstrate that these three gene products are involved in the urocortin induced protection of cardiac myocyte mitochondria. These proteins may interact at the mitochondria to produce the protective effect.

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Published date: 2004
Keywords: urocortin, cardioprotection, mitochondria, katp channel, ipla2, pkc?

Identifiers

Local EPrints ID: 24824
URI: http://eprints.soton.ac.uk/id/eprint/24824
ISSN: 0006-291X
PURE UUID: d81979d9-67a7-4cd2-9a33-ac3b205a9534

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Date deposited: 04 Apr 2006
Last modified: 15 Mar 2024 06:58

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Contributors

Author: Kevin M. Lawrence
Author: Paul A. Townsend
Author: Sean M. Davidson
Author: Christopher J. Carroll
Author: Simon Eaton
Author: Mike Hubank
Author: Richard A. Knight
Author: Anastasis Stephanou
Author: David S. Latchman

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