Apoptosis in Rat Cardiac Myocytes Induced by Fas Ligand: Priming for Fas-mediated Apoptosis with Doxorubicin

Yamaoka, Makoto; Yamaguchi, Seiji; Suzuki, Takahiko; Okuyama, Masaki; Nitobe, Joji; Nakamura, Norio; Mitsui, Youji; Tomoike, Hitonobu

doi:10.1006/jmcc.2000.1132

Cited by 82 publications

(57 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Specifically, rat-derived embryonic cardiomyocytes, which are normally resistant to FAS-L induced apoptosis [41], may get sensitized to FAS-L when pre-exposed to DOX [49,50]. Interestingly, DOX pre-exposure may also induce increased FAS-L released by rat-derived embryonic cardiomyocytes [41], suggesting a DOX-sensitization dependent autocrine/paracrine mechanism for cardiac apoptosis induction.…”

Section: Does Dox Exposure Change Apoptosis Likelihood To Later Somatmentioning

confidence: 99%

Doxorubicin-induced chronic dilated cardiomyopathy—the apoptosis hypothesis revisited

Kankeu

Clarke²,

Passante

et al. 2016

J Mol Med

View full text Add to dashboard Cite

The chemotherapeutic Doxorubicin (DOX) has significantly increased survival rates of pediatric and adult cancer patients. However, 10 % of pediatric cancer survivors will 10-20 years later develop severe Dilated Cardiomyopathy (DCM) and the exact molecular mechanisms of disease progression after this long latency time remain puzzling. We here revisit the hypothesis that elevated apoptosis signaling or its increased likelihood after DOX exposure can lead to an impairment of cardiac function and cause a cardiac dilation. Based on recent literature evidences, we first argue why even little detectable apoptosis may be sufficient to cause a dilated phenotype. We then review findings suggesting that mature cardiomyocytes are protected against DOX-induced apoptosis downstream, but not upstream to Mitochondrial Outer Membrane Permeabilisation (MOMP). This lack of prevention of MOMP-induction then is proposed to alter the metabolic phenotype, induce hypertrophic remodeling and lead to functional cardiac impairment even in absence of cardiomyocyte apoptosis. We further discuss findings that DOX exposure can lead to increased sensitivity to further cardiomyocyte apoptosis, which may cause a gradual loss in cardiomyocytes over time and a compensatory hypertrophic remodeling after treatment, potentially explaining the long lag time in disease onset. We finally note similarities between DOX-exposed cardiomyocytes and apoptosisprimed cancer cells and propose computational systems biology as tool to predict patient individual DOX doses. In conclusion, combining recent findings in rodent hearts and cardiomyocytes exposed to DOX with insights from apoptosis signal transduction allowed us to obtain a molecularly deeper insight in this delayed and still enigmatic pathology of DCM. Key messages1. Differentiated cardiomyocyte are protected to post but not pre-MOMP apoptosis 2. MOMP-induction can lead to cardiac hypertrophy and metabolic remodeling after DOX 3. DOX-exposed cardiomyocytes may be more sensitive to apoptosis over life time 4. DOX-exposed cardiomyocytes show similarities to apoptosis-primed cancer cells

show abstract

Section: Does Dox Exposure Change Apoptosis Likelihood To Later Somatmentioning

confidence: 99%

Doxorubicin-induced chronic dilated cardiomyopathy—the apoptosis hypothesis revisited

Kankeu

Clarke²,

Passante

et al. 2016

J Mol Med

View full text Add to dashboard Cite

show abstract

“…Studies have shown that treatment of DOX results in activation of apoptotic pathways in which caspase-3 is activated (Yamaoka et al, 2000;Kalivendi et al, 2001;2005;Jang et al, 2004). To examine the effect of Ca 2+ rise and ROS generation induced by DOX on cardiomyocytes, caspase-3 activity was determined.…”

Section: Caspase-3 Activation By Dox Is Inhibited By Ryr Blocker and mentioning

confidence: 99%

Doxorubicin-induced reactive oxygen species generation and intracellular Ca2+increase are reciprocally modulated in rat cardiomyocytes

Kim

Kim²,

Kim³

et al. 2006

Exp Mol Med

228

134

View full text Add to dashboard Cite

“…14 Several lines of evidence have suggested that oxidative stress alters cell survival and hypertrophic signals that lead to cardiomyocyte apoptosis and/or hypertrophy in isolated cardiomyocytes and in animals. 12,[15][16][17][18] Because oxidative stress after myocardial infarction was identified as playing a pivotal role for ventricular remodeling, we hypothesized that TLR-2 deficiency resulted in derangement of ventricular remodeling and preservation in cardiac function after myocardial infarction. To evaluate the potential role of TLR-2 on ventricular remodeling after myocardial infarction, we examined the effects of TLR-2 deficiency on cardiac function, structural aspects of ventricular remodeling, and survival rates after myocardial infarction in a mouse model.…”

mentioning

confidence: 99%

Toll-Like Receptor-2 Modulates Ventricular Remodeling After Myocardial Infarction

et al. 2003

Self Cite

View full text Add to dashboard Cite

show abstract

Apoptosis in Rat Cardiac Myocytes Induced by Fas Ligand: Priming for Fas-mediated Apoptosis with Doxorubicin

Cited by 82 publications

References 35 publications

Doxorubicin-induced chronic dilated cardiomyopathy—the apoptosis hypothesis revisited

Doxorubicin-induced chronic dilated cardiomyopathy—the apoptosis hypothesis revisited

Doxorubicin-induced reactive oxygen species generation and intracellular Ca2+increase are reciprocally modulated in rat cardiomyocytes

Toll-Like Receptor-2 Modulates Ventricular Remodeling After Myocardial Infarction

Contact Info

Product

Resources

About