Adenosine Prevents NF-κB Binding Activity Induced by Ischemia in Rat Heart

Adenosine prevents ischemic injury, induces preconditioning, and minimizes reperfasional damage. However, the beneficial mechanisms of adenosine in the cardiovascular system are not completely clear. The eukaryotic transcription factor NF-κB is activated by multiple stimuli and regulates many immediate-early gene expression involved in immune, inflammatory and defensive reactions. Ischemia rapidly induced NF-κB binding activity in rat heart was observed in our laboratory. The effect of adenosine (0.2 mM for 5 min) on NF-κB activation was studied in ischemic myocardium (0, 1, 2, 3, 4, 5, 7.5, 10, 15, and 30 min). Cytoplasmic and nuclear proteins were extracted for measuring IκBα levels and NF-κB binding activity. Western blot showed significant decrease of cytoplasmic IκBα during 3 to 7.5 min of ischemia while pretreating the hearts with adenosine prevented the loss of IκBα protein. Similarly, the activation and translocation of NF-κB due to myocardium ischemia (3 to 30 min) were blocked by adenosine. Northern blot hybridization also showed that adenosine maintained the normal levels of IκBα mRNA during the entire period of ischemia. The protective effect of adenosine and ischemia preconditioning may mediate through modulation of NF-κB activation which induces immediate-early gene expression that resulted in ischemic reperfusional injury