Blocking the development of postischemic cardiomyopathy with viral gene transfer of the apoptosis repressor with caspase recruitment domain

Chatterjee, Subhasis; Bish, Lawrence T.; Jayasankar, Vasant; Stewart, Allan; Woo, Y. Joseph; Crow, Michael T.; Gardner, Timothy J.; Sweeney, H. Lee

doi:10.1016/s0022-5223(02)73229-7

Cited by 42 publications

(34 citation statements)

References 23 publications

(25 reference statements)

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“…The present results confirmed this report and demonstrated that a moderate hypercholesterolemia (2% cholesterol diet for 8 weeks) also increased myocardial apoptosis. Several studies stated that inhibition of apoptosis by a variety of pharmacological and genetic approaches results in smaller infarction (Brocheriou et al, 2000;Mocanu et al, 2001) and improved cardiac function (Abbate et al, 2002;Chatterjee et al, 2003). Taurine, is known as to protect various disorders and has been demonstrated to have beneficial effects in nephropathy, cardiomyopathy and neuropathy, (Szymanski and Winiarska, 2008).…”

Section: Discussionmentioning

confidence: 99%

Taurine Attenuates Hepatic and Cardiac Damage and Apoptosis in Rabbits Fed a High-Fat Diet

Abdel-Rahman¹

2014

OnLine Journal of Biological Sciences

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A hypercholesterolemia diet has been associated with the hepatic and cardiac abnormalities and the pathological changes. The present work was designed to investigate the histological and immunohistochemical changes in the liver and heart of rabbits when fed high fat diet and the possible protective role of an antioxidant "taurine". Twenty-four male white New Zealand rabbits were divided into four groups, 6 rabbits each. Group 1, served as a control, rabbits fed with a normal diet. Group 2, (taurine group), rabbits were given orally taurine (10 mg Kg −1 b.w/day) for 8 weeks. Group 3 (hypercholesterolemic group), rabbits fed (2% cholesterol-enriched diet for 8 weeks. Group 4, rabbits fed 2% cholesterol-enriched diet plus taurine (10 mg Kg −1 b.w/day) orally for the same period. Histopathological examinations revealed that high cholesterol diet caused hepatic and myocardial tissue changes compared with rabbits fed with a normal diet. Including fatty degeneration, inflammations and necrosis of Hepatocytes and vacuolar degeneration, disorganization of myofibrils and necrosis of myocardial cells. Immunohistochemistry for caspase-3 for apoptosis were performed. Caspase-3 positive cells in the liver tissue and Caspase-3 positive area in myocardial tissue increased in high cholesterol diet group. Taurine markedly attenuate hypercholesterolemia-induced cardiac and hepatic histopathological changes in the cholesterol plus taurine group compared to the cholesterol group. Thus, the results suggest that taurine could play a beneficial role against hypercholesterolemiainduced complications in the liver and heart of the rabbits.

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Section: Discussionmentioning

confidence: 99%

Taurine Attenuates Hepatic and Cardiac Damage and Apoptosis in Rabbits Fed a High-Fat Diet

Abdel-Rahman¹

2014

OnLine Journal of Biological Sciences

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“…Inhibition of the intrinsic pathway involves interactions between ARC and the C-terminal regulatory domain of Bax (Bcl-2-associated X protein) that prevent the conformational activation of Bax and its translocation to the mitochondria in response to apoptotic stimuli (12,13). Overexpression of ARC blocks cell death in response to activators of both extrinsic and intrinsic pathways (9,(12)(13)(14)(15)(16)(17). Conversely, knock down of endogenous ARC promotes activation of both pathways (12).…”

mentioning

confidence: 99%

The Apoptosis Inhibitor ARC Undergoes Ubiquitin-Proteasomal-mediated Degradation in Response to Death Stimuli

Nam¹,

Mani²,

Wu³

et al. 2007

Journal of Biological Chemistry

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Efficient induction of apoptosis requires not only the activation of death-promoting proteins but also the inactivation of inhibitors of cell death. ARC (apoptosis repressor with caspase recruitment domain) is an endogenous inhibitor of apoptosis that antagonizes both central apoptosis pathways. Despite its potent inhibition of cell death, cells that express abundant ARC eventually succumb. A possible explanation is that ARC protein levels decrease dramatically in response to death stimuli. The mechanisms that mediate decreases in ARC protein levels during apoptosis and whether these decreases initiate the subsequent cell death are not known. Here we show that endogenous ARC protein levels decrease in response to death stimuli in a variety of cell contexts as well as in a model of myocardial ischemia-reperfusion in intact mice. Decreases in ARC protein levels are not explained by alterations in the abundance of ARC transcripts. Rather, pulse-chase experiments show that decreases in steady state ARC protein levels during apoptosis result from marked destabilization of ARC protein. ARC protein destabilization, in turn, is mediated by the ubiquitin-proteasomal pathway, as mutation of ARC ubiquitin acceptor residues stabilizes ARC protein and preserves its steady state levels during apoptosis. In addition, this degradation-resistant ARC mutant exhibits improved cytoprotection. We conclude that decreases in ARC protein levels in response to death stimuli are mediated by increased ARC protein degradation via the ubiquitin-proteasomal pathway. Moreover, these data demonstrate that decreases in ARC protein levels are a trigger, and not merely a consequence, of the ensuing cell death.

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“…This is supported by the observation that exogenous ARC reduces infarct size after ischemia/reperfusion (I/R) injury of isolated perfused rat hearts and blocks the development of postischemic cardiomyopathy. 13,14 Despite several overexpression studies on ARC, little is known about its endogenous function. However, this is of particular significance because exposure of cardiomyocytes to ischemia, hypoxia, or oxidative stress leads to a rapid downregulation of ARC protein levels with subsequent cell death in vitro, suggesting that decreasing ARC levels may function as a critical switch of cardiomyocyte survival.…”

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confidence: 99%

Apoptosis Repressor With Caspase Recruitment Domain Is Required for Cardioprotection in Response to Biomechanical and Ischemic Stress

et al. 2006

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on behalf of the German Heart Failure Network Background-Ischemic heart disease and heart failure are associated with an increased loss of cardiomyocytes due to apoptosis. Whether cardiomyocyte apoptosis plays a causal role in the pathogenesis of heart failure remains enigmatic. The apoptosis repressor with caspase recruitment domain (ARC) is a recently discovered antiapoptotic factor with a highly specific expression pattern in striated muscle and neurons. ARC is a master regulator of cardiac death signaling because it is the only known factor that specifically inhibits both the intrinsic and extrinsic apoptotic death pathway. In this study we attempted to elucidate the physiological role of ARC and to understand pathophysiological consequences resulting from its deletion. Methods and Results-We generated ARC-deficient mice, which developed normally to adulthood and had no abnormality in cardiac morphology and function under resting conditions. On biomechanical stress induced by aortic banding, ARC-deficient mice developed accelerated cardiomyopathy compared with littermate controls, which was characterized by reduced contractile function, cardiac enlargement, and myocardial fibrosis. Likewise, ischemia/ reperfusion injury of ARC-deficient mice resulted in markedly increased myocardial infarct sizes. Although in both instances a significant increase in apoptotic cardiomyocytes could be observed in ARC-deficient mice, neither in vitro nor in vivo studies revealed any effect of ARC on classic hypertrophic cardiomyocyte growth responses. The pathophysiological relevance of downregulated ARC levels was underscored by specimens from failing human hearts showing markedly reduced ARC protein levels. Conclusions-Our study identifies a tissue-specific antiapoptotic factor that is downregulated in human failing myocardium and that is required for cardioprotection in pressure overload and ischemia.

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Blocking the development of postischemic cardiomyopathy with viral gene transfer of the apoptosis repressor with caspase recruitment domain

Cited by 42 publications

References 23 publications

Taurine Attenuates Hepatic and Cardiac Damage and Apoptosis in Rabbits Fed a High-Fat Diet

Taurine Attenuates Hepatic and Cardiac Damage and Apoptosis in Rabbits Fed a High-Fat Diet

The Apoptosis Inhibitor ARC Undergoes Ubiquitin-Proteasomal-mediated Degradation in Response to Death Stimuli

Apoptosis Repressor With Caspase Recruitment Domain Is Required for Cardioprotection in Response to Biomechanical and Ischemic Stress

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