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Cardiovascular Research 2004 64(2):322-330; doi:10.1016/j.cardiores.2004.07.013
© 2004 by European Society of Cardiology
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Copyright © 2004, European Society of Cardiology

Role of microtubules in ischemic preconditioning against myocardial infarction

Yuichi Nakamura, Tetsuji Miura*, Atsushi Nakano, Yoshihiko Ichikawa, Toshiyuki Yano, Hironori Kobayashi, Yoshihiro Ikeda, Takayuki Miki and Kazuaki Shimamoto

Second Department of Internal Medicine, Sapporo Medical University, School of Medicine, South-1 West-16, Chuo-ku, Sapporo 060-8543, Japan

* Corresponding author. Tel.: +81 11 611 2111x3226; fax: +81 11 644 7958. Email address: miura{at}sapmed.ac.jp

Objective: The role of microtubules in ischemic preconditioning (PC) was investigated in isolated perfused rabbit hearts.

Methods: Myocardial infarction was induced by 30-min global ischemia and 2-h reperfusion, and infarct size was expressed as a percentage of the left ventricle (%IS/LV). Using separate groups of rabbits, ventricular biopsies were taken before and after PC for determination of protein kinase C (PKC) translocation and p38-mitogen-activated protein kinase (p38MAP kinase) activation. To depolymerize microtubules, we used two structurally different agents, colchicine (50 µM) and nocodazole (1 µM).

Results: PC with two cycles of 5-min ischemia/5-min reperfusion significantly reduced infarct size from 60.1±5.0% to 20.0±5.0%. Although neither colchicine nor nocodazole modified infarct size in nonpreconditioned hearts, these agents abolished the infarct size-limiting effects of PC (%IS/LV=56.1±6.0% and 53.5±2.5%, respectively). Colchicine prevented translocation of PKC-{varepsilon} and p38MAP kinase activation by PC. PKC translocation by infusion of 1-oleyl-2-acetyl-sn-glycerol in nonischemic hearts was also prevented by colchicine.

Conclusion: Microtubules play a crucial role in the development of anti-infarct tolerance by PC as a mechanism supporting translocation of activated PKC.

KEYWORDS Preconditioning; Microtubule; Protein kinase C; Infarct size

Time for primary review 15 days


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