Journal ArticleDOI
Cell Death in the Pathogenesis of Heart Disease: Mechanisms and Significance
Reads0
Chats0
TLDR
Pharmacological and genetic inhibition of apoptosis and necrosis lessens infarct size and improves cardiac function in these disorders and a better understanding of these processes and their interrelationships may allow for the development of novel therapies for the major heart syndromes.Abstract:
Cell death was once viewed as unregulated. It is now clear that at least a portion of cell death is a regulated cell suicide process. This type of death can exhibit multiple morphologies. One of these, apoptosis, has long been recognized to be actively mediated, and many of its underlying mechanisms have been elucidated. Moreover, necrosis, the traditional example of unregulated cell death, is also regulated in some instances. Autophagy is usually a survival mechanism but can occur in association with cell death. Little is known, however, about how autophagic cells die. Apoptosis, necrosis, and autophagy occur in cardiac myocytes during myocardial infarction, ischemia/reperfusion, and heart failure. Pharmacological and genetic inhibition of apoptosis and necrosis lessens infarct size and improves cardiac function in these disorders. The roles of autophagy in ischemia/reperfusion and heart failure are unresolved. A better understanding of these processes and their interrelationships may allow for the development of novel therapies for the major heart syndromes.read more
Citations
More filters
Journal ArticleDOI
Cardioprotective Role of Tumor Necrosis Factor Receptor-Associated Factor 2 by Suppressing Apoptosis and Necroptosis
TL;DR: An important Traf2-mediated, NF&kgr;B-independent, prosurvival pathway in the heart is identified by suppressing necroptotic signaling, which may serve as a new therapeutic target for pathological remodeling and heart failure.
Journal ArticleDOI
A small-molecule allosteric inhibitor of BAX protects against doxorubicin-induced cardiomyopathy
Dulguun Amgalan,Thomas P. Garner,Ryan Pekson,Xiaotong F. Jia,Mounica Yanamandala,Mounica Yanamandala,Victor Paulino,Felix G. Liang,J. Jose Corbalan,Jaehoon Lee,Yun Chen,George S. Karagiannis,Luis Rivera Sanchez,Luis Rivera Sanchez,Huizhi Liang,Swathi-Rao Narayanagari,Kelly Mitchell,Andrea Lopez,Victoria Margulets,Marco Scarlata,Gaetano Santulli,Aarti Asnani,Aarti Asnani,Randall T. Peterson,Randall T. Peterson,Rachel B. Hazan,John S. Condeelis,Maja H. Oktay,Ulrich Steidl,Lorrie A. Kirshenbaum,Evripidis Gavathiotis,Richard N. Kitsis +31 more
TL;DR: BAX is shown to be rate-limiting in doxorubicin-induced cardiomyopathy and a small-molecule BAX inhibitor is identified that blocks both apoptosis and necrosis to prevent this syndrome.
Journal ArticleDOI
Ginsenoside Rg1 inhibits autophagy in H9c2 cardiomyocytes exposed to hypoxia/reoxygenation
TL;DR: H/R induces autophagy in H9c2 cells leading to cell injury and Rg1 inhibits autophagosomal formation and apoptosis in the cells, which may be beneficial to the survival of cardiomyocytes under H/R.
Journal ArticleDOI
The Paradoxical Role of Inflammation in Cardiac Repair and Regeneration
Bingbing Jiang,Ronglih Liao +1 more
TL;DR: The hypothesis that temporally regulated activation and suppression of inflammation may be critical for achieving effective cardiac repair and regeneration is put forth.
Journal ArticleDOI
Autophagy in cigarette smoke-induced chronic obstructive pulmonary disease
TL;DR: Investigation of the potential role of macro-autophagy, a cellular homeostatic mechanism, in COPD and cigarette smoke-induced lung-cell injury found activation of autophagic proteins was associated with epithelial cell apoptosis in response to cigarette smoke, with pathogenic implications in COPd.
References
More filters
Journal ArticleDOI
Cytochrome c and dATP-Dependent Formation of Apaf-1/Caspase-9 Complex Initiates an Apoptotic Protease Cascade
Peng Li,Deepak Nijhawan,Imawati Budihardjo,Srinivasa M. Srinivasula,Manzoor Ahmad,Emad S. Alnemri,Xiaodong Wang +6 more
TL;DR: Mutation of the active site of caspase-9 attenuated the activation of cazase-3 and cellular apoptotic response in vivo, indicating that casp enzyme-9 is the most upstream member of the apoptotic protease cascade that is triggered by cytochrome c and dATP.
Journal ArticleDOI
Autophagy in the Pathogenesis of Disease
TL;DR: This Review summarizes recent advances in understanding the physiological functions of autophagy and its possible roles in the causation and prevention of human diseases.
Journal ArticleDOI
The Release of Cytochrome c from Mitochondria: A Primary Site for Bcl-2 Regulation of Apoptosis
TL;DR: In a cell-free apoptosis system, mitochondria spontaneously released cytochrome c, which activated DEVD-specific caspases, leading to fodrin cleavage and apoptotic nuclear morphology, and Bcl-2 acts to inhibit cy tochrome c translocation, thereby blocking caspase activation and the apoptotic process.
Journal ArticleDOI
Cleavage of BID by Caspase 8 Mediates the Mitochondrial Damage in the Fas Pathway of Apoptosis
TL;DR: The results indicate that BID is a mediator of mitochondrial damage induced by Casp8, and coexpression of BclxL inhibits all the apoptotic changes induced by tBID.
Journal ArticleDOI
The BCL-2 protein family: opposing activities that mediate cell death
TL;DR: New insights into interactions among BCL-2 family proteins reveal how these proteins are regulated, but a unifying hypothesis for the mechanisms they use to activate caspases remains elusive.