Premium
Cardioprotection mediated by urocortin is dependent upon PKCε activation
Author(s) -
Lawrence Kevin M.,
Kabir Alamgir M. N.,
Bellahcene Mohamed,
Davidson Sean,
Mesquita Rui S.,
Cao Xuebin,
McCormick James,
Carroll Christopher J.,
Chanalaris Anastasios,
Townsend Paul A.,
Hubank Mike,
Stephanou Anastasis,
Knight Richard A.,
Marber Michael S.,
Latchman David S.
Publication year - 2005
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.04-2506fje
Subject(s) - cardioprotection , urocortin , protein kinase c , ex vivo , in vivo , microbiology and biotechnology , effector , chemistry , reperfusion injury , pharmacology , kinase , in vitro , biology , ischemia , medicine , biochemistry , receptor
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 (PKCε) 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 PKCε in vitro and in the Langendorff perfused ex vivo heart. The importance of the PKCε isozyme in cardioprotection and its relationship to cardioprotection produced by Ucn was assessed using PKCε‐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 PKCε knockout mice. These findings indicate that the cardioprotective effect of Ucn is dependent upon PKCε.