Signal transduction in ischemic preconditioning: the role of kinases and mitochondrial K(ATP) channels.
Ischemic preconditioning is a phenomenon whereby exposure of the myocardium to a brief episode of ischemia and reperfusion markedly reduces tissue necrosis induced by a subsequent prolonged ischemia. Therefore, it is hoped that elucidation of the mechanism of preconditioning will yield therapeutic strategies capable of reducing myocardial infarction. In the rabbit, the brief period of preconditioning ischemia and reperfusion releases adenosine, bradykinin, opioids, and oxygen radicals that summate to induce the translocation and activation of protein kinase C (PKC). PKC appears to be the first element of a complex kinase cascade that is activated during the prolonged ischemia in preconditioned hearts. Current evidence indicates that PKC activates a tyrosine kinase that leads to the activation of p38 mitogen-activated protein (MAP) kinase or JNK, or possibly both. The stimulation of these stress-activated protein kinases ultimately induces the opening of mitochondrial K(ATP) channels that may be the final mediator of protection by ischemic preconditioning.
Baines
C P
CP
Department of Physiology, University of South Alabama, College of Medicine, Mobile 36688, USA.
Cohen
M V
MV
Downey
J M
JM
D000818:Animals; D015415:Biomarkers; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial; D008929:Mitochondria, Heart / Q000201:enzymology*; D017202:Myocardial Ischemia / Q000201:enzymology / Q000517:prevention & control; D015221:Potassium Channels / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011817:Rabbits; D015398:Signal Transduction / Q000502:physiology*
D015415:Biomarkers; D015221:Potassium Channels; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C