title: STRESS signaling pathways that modulate cardiac myocyte apoptosis.
abstract: The heart is a dynamic organ capable of significant architectural remodeling, cellular adaptations, and molecular reprogramming following both physiologic and pathologic stimulation. These whole organ and cellular adaptations are typically initiated by stress-responsive signaling pathways, which serve as central transducers of cardiac hypertrophic growth and/or ventricular dilation. In addition to initiating and maintaining phenotypic alterations in cardiac structure and function, stress-responsive signaling pathways have also been implicated in affecting the decision of myocytes to either survive or undergo programmed cell death (apoptosis). Indeed, necrosis or apoptosis of individual myocytes has become appreciated as yet another maladaptive event that negatively impacts the myocardium and its propensity towards failure. Here we will discuss the known associations between select stress-induced and neuroendocrine-mediated signaling pathways and regulation of cardiac myocyte survival or cell death. These signaling pathways include the extracellular signal-regulated protein kinases (ERK), p38 mitogen-activated protein kinases (MAPK), c-Jun NH2-terminal kinases (JNK), protein kinase C (PKC) isoforms, the protein phosphatase calcineurin, as well as a select group of additional kinases such as Janus kinase (JAK). While a fair amount of discordance exists in the literature, we will weigh evidence that largely suggests a pro-apoptotic regulatory role for the p38 mitogen-activated protein kinase, JNK, and PKCdelta, yet an anti-apoptotic regulatory role for ERK, PKCepsilon, JAK, and calcineurin in the myocardium.
authors.affiliation: Division of Molecular Cardiovascular Biology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Baines
authors.forename: Jeffery D
authors.initials: JD
authors.lastname: Molkentin
mesh_terms: D000818:Animals; D017209:Apoptosis; D019703:Calcineurin / Q000378:metabolism; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism*; D015398:Signal Transduction; D013312:Stress, Physiological / Q000503:physiopathology
chemical_list: D020928:Mitogen-Activated Protein Kinases; D019703:Calcineurin