Upstream signaling of protein kinase C-ε in xenon-induced pharmacological preconditioning: Implication of mitochondrial adenosine triphosphate dependent potassium channels and phosphatidylinositol-dependent kinase-1

Abstract

Xenon elicits preconditioning of the myocardium via protein kinase C-ε. We determined the implication of (1) the mitochondrial adenosinetriphosphate dependent potassium (K ATP) channels and (2) the 3′phosphatidylinositol-dependent kinase-1 (PDK-1) in activating protein kinase C-ε. For infarct size measurements, anaesthetized rats were subjected to 25 min of coronary artery occlusion followed by 120 min of reperfusion. Rats received xenon 70% during three 5-min periods before ischaemia with or without the K ATP channel blocker 5-hydroxydecanoate or Wortmannin as PI 3K/PDK-1 inhibitor. For Western blot, hearts were excised at five time points after xenon preconditioning (Control, 15, 25, 35, 45 min). Infarct size was reduced from 42 ± 6% (mean ± S.D.) to 27 ± 8% after xenon preconditioning ( P < 0.05). Western blot revealed an increased activation of PKC-ε after 45 min and of PDK-1 after 25 min during xenon preconditioning. 5-hydroxydecanoate and Wortmannin blocked both effects. PKC-ε is activated downstream of mitochondrial K ATP channels and PDK-1. Both pathways are functionally involved in xenon preconditioning.