Delayed cardioprotection in a human cardiomyocyte-derived cell line: the role of adenosine, p38MAP kinase and mitochondrial K-ATP.
BASIC RES CARDIOL
243 - 249.
Evidence of delayed preconditioning (PC) in man is limited. Adenosine is proposed as a trigger via action on the A(1) receptor in many species and the mitochondrial K-ATP channel is a likely end effector. We examined the ability of a brief, simulated ischemic episode on day one to provide delayed cardioprotection against lethal, simulated ischemia on day two in a human cardiac cell line with reference to the role of adenosine, the p38MAP kinase signalling pathway and mitochondrial K-ATP channel. ATPResults: PC and adenosine administered on day 1 protected against cell death on day 2 as measured by LDH release and propidium iodide (PI) exclusion: (%LDH release: PC: 12.1 +/- 1.1 %, ADO: 11.9 +/- 2.0 % vs control: 36.4 +/- 1.1 %; %PI positive: PC: 14.6 +/- 1.4 %, ADO: 17.9 +/- 2.0 % vs control: 34.4 +/- 2.0 % respectively). This protection is abolished by treatment with SB203580 prior to the protective stimulus on day 1: [PC + SB (%LDH release 28.6 +/- 2.8 %; %PI positive 34.7 +/- 2.2 %) and ADO + SB (%LDH release 25.3 +/- 2.9 %; %PI positive 33.7 +/- 7.3)]. Similarly 5-hydroxydecanoate abolished protection, when given immediately prior to lethal simulated ischemia on day 2: [PC + 5-HD; (%LDH release 31.9 +/- 4.8%; %PI positive 29.5 +/- 2.0 %) and ADO + 5-HD (%LDH release 36.9 +/- 4.0 %; %PI positive 34.8 +/- 2 %)].Conclusion: In this model delayed PC can be mimicked by adenosine and involves the p38MAP kinase pathway and the mitochondrial K-ATP channel.
|Title:||Delayed cardioprotection in a human cardiomyocyte-derived cell line: the role of adenosine, p38MAP kinase and mitochondrial K-ATP|
|Keywords:||preconditioning, adenosine, mitochondrial K-ATP, hypoxia/reoxygenation, ACTIVATED PROTEIN-KINASES, MYOCARDIAL PROTECTION, SIMULATED ISCHEMIA, RABBIT HEART, A(3) RECEPTORS, MAP KINASE, A(1), POTASSIUM, CHANNELS, STRESS|
|UCL classification:||UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
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