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Cardiovascular Research 2004 61(3):610-619; doi:10.1016/j.cardiores.2003.10.022
© 2004 by European Society of Cardiology
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Copyright © 2003, European Society of Cardiology

Ischemic preconditioning activates AMPK in a PKC-dependent manner and induces GLUT4 up-regulation in the late phase of cardioprotection

Yasuhiro Nishinoa, Tetsuji Miura*,a, Takayuki Mikia, Jun Sakamotoa,b, Yuichi Nakamuraa, Yoshihiro Ikedaa, Hironori Kobayashia and Kazuaki Shimamotoa

aSecond Department of Internal Medicine, Sapporo Medical University School of Medicine, South-1 west-1, Chou-ku Sapparo 060-8543, Japan
bDepartment of Pharmacology Sapporo Medical University School of Medicine South-1 west-1, Chou-ku Sapparo 060-8543, Japan

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

Objective: The aim of this study was to determine the role of AMP-activated protein kinase (AMPK) and its link to protein kinase C (PKC) in the late phase of cardioprotection afforded by ischemic preconditioning (PC) against myocardial stunning. Methods and results: Rabbits were instrumented with a balloon occluder around a coronary artery and with a Doppler sensor to monitor the thickening fraction (TF). Conscious rabbits underwent five cycles of 5-min ischemia/5-min reperfusion (I/R) on 2 consecutive days (days 1 and 2). Reduction of TF after I/R was significantly less and recovery of TF was faster on day 2, indicating a late PC effect. PC provoked translocation of PKC-{varepsilon} from the cytosol to the membrane and significantly increased AMPK activity by 100% immediately after PC. The mRNA level of GLUT4, a glucose transporter, was elevated by 150% at 3 h after PC, and the total protein level of GLUT4 was increased by 107% at 24 h after PC. The level of sarcolemmal GLUT4 protein after I/R on day 2 was 41% higher than its level after I/R on day 1. AMPK activation and up-regulation of GLUT4 by PC were abrogated by pre-treatment with PKC inhibitors. Conclusion: PC activated AMPK and up-regulated GLUT4 expression in a PKC-dependent manner. This GLUT4 up-regulation at 24 h after PC may contribute to attenuation of myocardial stunning.

KEYWORDS Ischemia; Preconditioning; Protein kinases; Stunning


Time for primary review 00 days


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