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Cardioprotection initiated by reactive oxygen species is dependent on activation of PKCepsilon.

Kabir, AMN; Clark, JE; Tanno, M; Cao, X; Hothersall, JS; Dashnyam, S; Gorog, DA; ... Marber, MS; + view all (2006) Cardioprotection initiated by reactive oxygen species is dependent on activation of PKCepsilon. Am J Physiol Heart Circ Physiol , 291 (4) H1893-H1899. 10.1152/ajpheart.00798.2005.

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To examine whether cardioprotection initiated by reactive oxygen species (ROS) is dependent on protein kinase Cepsilon (PKCepsilon), isolated buffer-perfused mouse hearts were randomized to four groups: 1) antimycin A (AA) (0.1 microg/ml) for 3 min followed by 10 min washout and then 30 min global ischemia (I) and 2 h reperfusion (R); 2) controls of I/R alone; 3) AA bracketed with 13 min of N-2-mercaptopropionyl- glycine (MPG) followed by I/R; and 4) MPG (200 microM) alone, followed by I/R. Isolated adult rat ventricular myocytes (ARVM) were exposed to AA (0.1 microg/ml), and lucigenin was used to measure ROS production. Murine hearts and ARVM were exposed to AA (0.1 microg/ml) with or without MPG, and PKCepsilon translocation was measured by cell fractionation and subsequent Western blot analysis. Finally, the dependence of AA protection on PKCepsilon was determined by the use of knockout mice (-/-) lacking PKCepsilon. AA exposure caused ROS production, which was abolished by the mitochondrial uncoupler mesoxalonitrile 4-trifluoromethoxyphenylhydrazone. In addition, AA significantly reduced the percent infarction-left ventricular volume compared with control I/R (26 +/- 4 vs. 43 +/- 2%; P < 0.05). Bracketing AA with MPG caused a loss of protection (52 +/- 7 vs. 26 +/- 4%; P < 0.05). AA caused PKCepsilon translocation only in the absence of MPG, and protection was lost on the pkcepsilon(-/-) background (38 +/- 3 vs. 15 +/- 4%; P < 0.001). AA causes ROS production, on which protection and PKCepsilon translocation depend. In addition, protection is absent in PKCepsilon null hearts. Our results imply that, in common with ischemic preconditioning, PKCepsilon is crucial to ROS-mediated protection.

Type: Article
Title: Cardioprotection initiated by reactive oxygen species is dependent on activation of PKCepsilon.
Location: United States
DOI: 10.1152/ajpheart.00798.2005
Keywords: Animals, Anti-Bacterial Agents, Antimycin A, Cells, Cultured, Enzyme Activation, Female, Gene Expression Regulation, Enzymologic, Ischemic Preconditioning, Myocardial, Male, Mice, Mice, Knockout, Mitochondria, Heart, Myocytes, Cardiac, Protein Kinase C-epsilon, Random Allocation, Rats, Reactive Oxygen Species, Reperfusion Injury
UCL classification: UCL > Office of the President and Provost
UCL > School of Life and Medical Sciences > Faculty of Medical Sciences
URI: http://discovery.ucl.ac.uk/id/eprint/183298
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