Role of mitogen-activated protein kinases in ischemia and reperfusion injury : the good and the bad.

Abstract

There is growing evidence that multiple mitogen-activated protein (MAP) kinases are activated during ischemia and/or reperfusion and may contribute to the structural and functional changes after myocardial ischemia. A new study by Yue et al1 in this issue of Circulation Research attempts to address the role of MAP kinases in ischemic myocardium and suggests that ERK1/ERK2 is part of a “survival” pathway whereas p38 and JNK mediate a “death” pathway in the ischemic myocardium. Myocyte loss during the acute stage of myocardial infarction involves both apoptotic and necrotic cell death.2 3 4 Therefore, it is reasonable to think that the balance of cell survival and death is critical during the pathological evolution of postischemic cardiac dysfunction. Recently, many scientists seeking to elucidate the intricate relationship between signal transduction and this balance of survival and death in ischemic myocardium have focused on MAP kinases. MAP kinases are highly conserved serine/threonine kinases that are activated in response to a wide variety of stimuli including growth factors, G protein–coupled receptors, and environmental stresses.5 Consequently, they play a role in numerous cell functions including growth and proliferation. The MAP kinases themselves require dual phosphorylation on a Thr-X-Tyr motif to become active. Three major MAP kinase cascades have been extensively studied in the heart: extracellular signal–regulated kinases (ERK1 and ERK2), c-Jun N-terminal kinases (JNK1 and JNK2), and p38 kinases, of which the p38α and p38β isoforms are found in the heart.5 Recently, a fourth MAP …