Death Receptor Signaling in the Heart: Cell Survival, Apoptosis, and Necroptosis

摘要: Article, see p 729 Research over the past 3 decades has established that loss of cardiomyocytes through regulated cell suicide mechanisms contributes critically to pathogenesis myocardial infarction, heart failure, and other cardiac syndromes.1 Two most important death programs in context disease are apoptosis necrosis. These forms differ primarily with respect magnitude collateral damage inflicted on surrounding tissue. In apoptosis, plasma membrane remains intact until dying undergoes phagocytosis, whereas necrosis not only does become leaky, but actively secretes proinflammatory molecules. Apoptosis always been recognized as a gene-directed process. contrast, was thought be an uncontrolled form resulting from overwhelming physical chemical trauma cell. A big surprise 15 years, however, realization significant proportion necrotic deaths occurs highly mechanisms. Both can initiated 2 major pathways: 1 involving mitochondria surface receptors (Figure, A). this issue Circulation , Guo et al2 utilize multiple mouse genetic models dissect receptor pathway heart. The finding study is knockout gene encoding tumor factor receptor-associated (TRAF2), protein pathway, results dilated cardiomyopathy unleashing apoptotic cardiomyocyte death. Figure. Apoptosis signaling. Overview mitochondrial pathways. Both Regardless defining molecular event activation caspases, which class cysteine proteases. Caspase takes place …