Ischemia-induced translocation of protein kinase C-epsilon mediates cardioprotection in the streptozotocin-induced diabetic rat.
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.
Department of Laboratory Medicine, Oita Medical University, Hasama, Japan.
Tatsuhiko
T
Ooie
Naohiko
N
Takahashi
Tomoko
T
Nawata
Masaya
M
Arikawa
Kunitoshi
K
Yamanaka
Munetaka
M
Kajimoto
Tetsuji
T
Shinohara
Sakuji
S
Shigematsu
Masahide
M
Hara
Hironobu
H
Yoshimatsu
Tetsunori
T
Saikawa
D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac; D002302:Cardiac Output; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism / Q000502:physiology; D017202:Myocardial Ischemia / Q000201:enzymology*; D011493:Protein Kinase C / Q000378:metabolism* / Q000502:physiology*; D051744:Protein Kinase C-epsilon; D021381:Protein Transport; D051381:Rats; D015427:Reperfusion Injury / Q000201:enzymology
D004791:Enzyme Inhibitors; D007527:Isoenzymes; C497257:Prkce protein, rat; D011493:Protein Kinase C; D051744:Protein Kinase C-epsilon