Signaling networks regulating cardiac myocyte survival and death.
In conditions of stress, cardiomyocytes mount an adaptive response that attempts to normalize ventricular wall stress and maintain cardiac output. Prolonged stress overwhelms this protective response and leads to the apoptosis of cardiomyocytes and heart failure. The balance between the protective and apoptotic mechanisms is determined by a network of signaling pathways that can interact with the JAK/STAT pathway to effect the expression of either cardioprotective or pro-apoptotic genes. The activation of STAT3 affords cardioprotection, whereas activation of STAT1 is associated with apoptosis. Full and sustained activation of either pathway benefits from the cross-activation of the STATs by serine/threonine kinases in collateral signaling pathways. These pathways are activated by cytokines such as TNFalpha, Fas ligand and G-protein-coupled receptor ligands released by the ischemic myocardium. The interaction of these ligands with their respective signal transduction pathways and the nature of their interaction with the JAK/STAT pathway can influence the fate of stressed cardiomyocytes.
Wagner
Michael
M
State University of New York Downstate Medical Center, Center for Cardiovascular and Muscle Research, Department of Cell Biology, 450 Clarkson Avenue, Brooklyn, NY 11203, USA. michael.wagner@downstate.edu
Siddiqui
M Aq
MA
D017209:Apoptosis; D016923:Cell Death; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D015428:Myocardial Reperfusion Injury / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D016207:Cytokines; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; C494092:STAT5A protein, human; D025521:Tumor Suppressor Proteins