The present study investigated the role of translocation of
protein kinase C (PKC) during
ischemia/reperfusion in cardioprotection in the
streptozotocin (STZ)-induced diabetic rat. Twelve weeks after injection of STZ or vehicle, male Wister-King rat hearts were isolated and perfused in the presence or absence of 50 nmol/L
staurosporine or 2 mumol/L
chelerythrine using a Langendorff apparatus. Thirty minutes of global
ischemia was followed by the same period of reperfusion. The time to onset of
contracture was determined during
ischemia. The recovery of left ventricular function, incidence of
ventricular tachycardia/fibrillation (VT/VF), and amount of released
creatine kinase (CK) were determined during the reperfusion period. Translocation of the PKC-alpha, -beta, -delta and -epsilon
isoforms was determined by immunoblotting. Development of
contracture was delayed, the recovery of left ventricular function was greater, and the incidence of VT/VF and amount of released CK were lower in diabetic than in control hearts.
Ischemia caused an increase in the particulate/cytosolic fraction ratio of the
PKC- epsilon isoform in the diabetic and control hearts. However, this translocation of
PKC-epsilon during
ischemia was transient in the control heart, but was persistent in the diabetic heart. The
ischemia-induced translocation of
PKC-epsilon was abolished by
chelerythrine perfusion. These results suggest that persistent translocation of
PKC-epsilon during
ischemia plays a major role in cardioprotection against
ischemia/reperfusion injury in STZ-induced diabetic rats.