Dynamism of NF-κB and AP-1 activation in the signal transduction of ischaemic myocardial preconditioning

Abstract

Nuclear factor (NF)-κB and activation protein (AP)-1 transcription factors play an important role in the signal transduction of delayed ischaemic preconditioning (PC) leading to myocardial cytoprotection. Because the exact mechanism of the activation of these factors is still not clear, we aimed to monitor the time fluctuation of NF-κB and AP-1 induction in an in vivo animal model. Furthermore, we measured the induction rate of these factors using repeated cycles of PC. Following median thoracotomy, anaesthetized animals (24 New Zealand White rabbits) were subjected to ischaemic PC by occlusion of the left anterior descending coronary artery for 5 min. After 10 and 30 min, and 1, 2, 3 and 4 h of reperfusion, tissue samples were taken from the ischaemic myocardium, and the DNA binding activity of the transcription factors was measured with electrophoretic mobility shift assay. A further 12 animals were subjected to 2 x, 3 x or 4 x 5-min ischaemic PC, and after a 30-min or 1-hour reperfusion period, we investigated the possible modulation of NF-κB and AP-1 induction. Our results show significant, biphasically increased NF-κB activity with peak levels at 30 min and 3 h of reperfusion in preconditioned myocardium. AP-1 increased monophasically, with the peak level at 1 h of reperfusion. Repeated PC stimuli enhanced the activity of both transcription factors analyzed, but there was no significant correlation between the number of cycles and the rate of activation. Our results show that the activation of NF-κB and AP-1 have a specific time curve, and the induction of these factors is only slightly influenced by the number of PC cycles. Copyright © 2004 S. Karger AG, Basel.