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- 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.
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- 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.
Authors: Raymond K Kudej; Mathew Fasano; Xin Zhao; Gary D Lopaschuk; Susan K Fischer; Dorothy E Vatner; Stephen F Vatner; E Douglas Lewandowski Journal: Cardiovasc Res Date: 2011-08-11 Impact factor: 10.787
Authors: Karla Bianca Neves; Aurelie Nguyen Dinh Cat; Rheure Alves-Lopes; Katie Yates Harvey; Rafael Menezes da Costa; Nubia Souza Lobato; Augusto Cesar Montezano; Ana Maria de Oliveira; Rhian M Touyz; Rita C Tostes Journal: Am J Physiol Heart Circ Physiol Date: 2018-09-14 Impact factor: 4.733
Authors: Makhosazane Zungu; Jonathan C Schisler; M Faadiel Essop; Chris McCudden; Cam Patterson; Monte S Willis Journal: Am J Pathol Date: 2010-12-23 Impact factor: 4.307
Authors: Ji Li; Dake Qi; Haiying Cheng; Xiaoyue Hu; Edward J Miller; Xiaohong Wu; Kerry S Russell; Nicole Mikush; Jiasheng Zhang; Lei Xiao; Robert S Sherwin; Lawrence H Young Journal: Proc Natl Acad Sci U S A Date: 2013-09-16 Impact factor: 11.205