Circulation Research. 2004;94:7-16
doi: 10.1161/01.RES.0000108082.76667.F4
doi: 10.1161/01.RES.0000108082.76667.F4
© 2004 American Heart Association, Inc.
Reviews |
Primary and Secondary Signaling Pathways in Early Preconditioning That Converge on the Mitochondria to Produce Cardioprotection
From the Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, US Department of Health and Human Services, Research Triangle Park, NC.
Correspondence to Elizabeth Murphy, Mail Drop F2-07, Box 12233, Research Triangle Park, NC 27709. E-mail murphy1{at}niehs.nih.gov
This Review is part of a thematic series on Mitochondrial Dysfunction in Ischemia, which includes the following articles:
Role of the Mitochondrial Permeability Transition in Myocardial Disease
Primary and Secondary Signaling Pathways in Early Preconditioning That Converge on the Mitochondria to Produce Cardioprotection
Evidence for Mitochondrial K+ Channels and Their Role in Cardioprotection
Mitochondrial Death Pathways
Roberto Bolli Editor
Cardioprotective mechanisms such as acute or early preconditioning activate several primary signaling pathways that seem to converge on mitochondrial targets, leading to altered cell metabolism and inhibition of apoptosis. Acute preconditioning leads to generation of agonists, which bind to G protein–coupled receptors, and initiates a signaling cascade that involves activation of phosphoinositide-3-kinase, endothelial NO synthase, protein kinase C, glycogen synthase kinase 3ß, mitogen-activated protein kinases, and other signaling pathways. Activation of these signaling pathways along with generation of reactive oxygen species leads to alterations in the activity of key mitochondrial proteins such as mitochondrial ATP-sensitive K+ channels, the mitochondrial permeability transition pore, and bcl-2 family members. Alterations in these mitochondrial proteins results in altered metabolism and inhibition of cell death, thus resulting in cardioprotection.
Key Words: apoptosis • cardioprotection • signaling pathways • preconditioning • mitochondria
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