Pretreatment with tyrosine kinase inhibitor attenuates the reduction of apoptosis 24 h after ischemic preconditioning.
We investigated whether ischemic preconditioning (PC) attenuates ischemia/reperfusion-induced injury in part by decreasing apoptosis and whether tyrosine kinase (TK) can regulate the signaling pathway leading to apoptosis in delayed cardioprotection. Six groups of rabbits were studied in the early phase (EP) and in the delayed phase (DP): (1) sham-operated control animals were received vehicle only (Veh-sham); (2) rabbits that received I.V. genistein (a nonspecific TK inhibitor) 10 min before ischemia (Gen-sham); (3) rabbits that received I.V. daidzein (an inactive structural analog of genistein) 10 min before ischemia (Dzn-sham); (4) rabbits preconditioned with 4 cycles of 5-min occlusion of left anterior descending coronary artery (LAD) and 10-min reperfusion (PC); (5) rabbits that received I.V. genistein, 10 min before PC (Gen-PC); (6) rabbits that received I.V. daidzein 10 min before PC (Dzn-PC). All rabbits underwent 30-min ischemia followed by 180-min reperfusion. Infarct size in the PC, Gen-PC, and Dzn-PC groups in the EP was significantly (p < 0.0001) reduced relative to controls Gen and Dzn. Delayed cardioprotection was blocked significantly (p < 0.0001) by genistein. In the EP, apoptosis was significantly (p < 0.0001) decreased in PC, Gen-PC, and Dzn-PC groups relative to controls Gen and Dzn. In the DP, a reduction of apoptosis was not seen in the Gen-PC group. This study suggests that PC reduces ischemic injury in part by decreasing apoptosis after ischemia/reperfusion and also that TK phosphorylation is involved in the signal transduction cascade leading to the decline of apoptosis in the DP.
Okubo
Shinji
S
Department of Cardiology, Kanazawa Medical University, Uchinada, Kahoku-gun, Ishikawa, 920-0293 Japan. shinkubo@kanazawa-med.ac.jp
Tanabe
Yujirou
Y
Takeda
Kenji
K
Kitayama
Michihiko
M
Kanemitsu
Seiyu
S
Kukreja
Rakesh C
RC
Takekoshi
Noboru
N
D000818:Animals; D017209:Apoptosis; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D019833:Genistein / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D009203:Myocardial Infarction / Q000150:complications* / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000503:physiopathology* / Q000517:prevention & control*; D015425:Myocardial Reperfusion; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D011817:Rabbits; D015398:Signal Transduction
D004791:Enzyme Inhibitors; D019833:Genistein; D011505:Protein-Tyrosine Kinases