Cardiomyocyte survivin protein expression is associated with cell size and DNA content in the failing human heart and is reversibly regulated after ventricular unloading

Wohlschlaeger, Jeremias; Meier, Birgit; Schmitz, Klaus; Takeda, Atsushi; Takeda, Nobuakira; Vahlhaus, Christian; Levkau, Bodo; Stypmann, Jörg; Schmid, Çhristof; Schmid, Kurt Werner; Baba, Hideo A.

doi:10.1016/j.healun.2010.06.015

Cited by 14 publications

(5 citation statements)

References 20 publications

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“…Cardiac-specific deletion of survivin results in premature cardiac death due to a dramatic reduction in cardiac myocyte numbers [ 20 ]. In addition, survivin is associated with cardiac myocyte size and DNA content in the failing human heart [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Insulin Protects Cardiac Myocytes from Doxorubicin Toxicity by Sp1-Mediated Transactivation of Survivin

Lee

Kang

et al. 2015

PLoS ONE

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Insulin inhibits ischemia/reperfusion-induced myocardial apoptosis through the PI3K/Akt/mTOR pathway. Survivin is a key regulator of anti-apoptosis against doxorubicin-induced cardiotoxicity. Insulin increases survivin expression in cardiac myocytes to mediate cytoprotection. However, the mechanism by which survivin mediates the protective effect of insulin against doxorubicin-associated injury remains to be determined. In this study, we demonstrated that pretreatment of H9c2 cardiac myocytes with insulin resulted in a significant decrease in doxorubicin-induced apoptotic cell death by reducing cytochrome c release and caspase-3 activation. Doxorubicin-induced reduction of survivin mRNA and protein levels was also significantly perturbed by insulin pretreatment. Reducing survivin expression with survivin siRNA abrogated insulin-mediated inhibition of caspase-3 activation, suggesting that insulin signals to survivin inhibited caspase-3 activation. Interestingly, pretreatment of H9c2 cells with insulin or MG132, a proteasome inhibitor, inhibited doxorubicin-induced degradation of the transcription factor Sp1. ChIP assay showed that pretreatment with insulin inhibited doxorubicin-stimulated Sp1 dissociation from the survivin promoter. Finally using pharmacological inhibitors of the PI3K pathway, we showed that insulin-mediated activation of the PI3K/Akt/mTORC1 pathway prevented doxorubicin-induced proteasome-mediated degradation of Sp1. Taken together, insulin pretreatment confers a protective effect against doxorubicin-induced cardiotoxicity by promoting Sp1-mediated transactivation of survivin to inhibit apoptosis. Our study is the first to define a role for survivin in cellular protection by insulin against doxorubicin-associated injury and show that Sp1 is a critical factor in the transcriptional regulation of survivin.

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Section: Introductionmentioning

confidence: 99%

Insulin Protects Cardiac Myocytes from Doxorubicin Toxicity by Sp1-Mediated Transactivation of Survivin

Lee

Kang

et al. 2015

PLoS ONE

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“…These data might also prompt further investigations to study the effect of survivin inhibitors in animal models of CHF. 45 The most important clinical issue involves the impact of the type of LV unloading-pulsatile or continuous-on the recovery and weaning rate. There are some trends in reduced recovery rate in patients supported with continuousflow devices, but the data are too scarce to draw meaningful conclusions.…”

Section: Weaningmentioning

confidence: 99%

Advances in mechanical circulatory support: Year in review

Potapov

Krabatsch

Ventura

et al. 2011

The Journal of Heart and Lung Transplantation

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“…Therefore, TCM may play a role in disease management via the AMPK pathway. Wohlschlaeger et al (2010) reported that the mean percentage of cardiomyocytes showing immunoreactivity against cyclin D1 significantly increased in patients with congestive HF compared with controls. Additionally, the silencing of lncRNA GAS5 attenuates hypoxia-induced cell death in HF, which is associated with the upregulated expression of the cyclin D1 gene (Du et al, 2019), these findings suggest that cyclin D1 may play a vital role in HF.…”

Section: Discussionmentioning

confidence: 99%

Cornus officinalis Sieb. et Zucc. Alleviates Mitochondrial Abnormalities and Heart Failure through AMPK

Chen,

Chen

et al. 2023

Pharmacognosy Magazine

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Background: Traditional Chinese medicine (TCM) has clear advantages in stabilizing patients with heart failure (HF) and improving cardiac functions. Aims: This study aimed to investigate the role of Cornus officinalis Sieb. et Zucc. (Cor) in HF. Settings and Design: Rats with HF were treated with Cor or Cor with an adenosine monophosphate-activated protein kinase (AMPK) inhibitor, dorsomorphin dihydrochloride (Dor). Materials and Methods: The weight and echocardiography findings of the rats were examined. AMPK and p-AMPK expression levels were assessed using Western blots, mitochondrial changes were evaluated using transmission electron microscopy (TEM), and adenosine triphosphate (ATP) levels were detected in each group. Finally, the targets of Cor were analyzed using HERB ( http://herb.ac.cn ). Statistical Analysis Used: A Student’s t-test was used to compare two groups, and a one-way analysis of variance was performed for intergroup comparison. A p < 0.05 indicated that the difference was statistically significant. Results: Compared with that of the Sham group, the body weight of the Model group decreased; left ventricular end diastolic diameter (LVIDd) and left ventricular end systolic diameter (LVIDs) increased; and left ventricular end diastolic posterior wall thickness (LVPWd), left ventricular end systolic posterior wall thickness (LVPWs), left ventricular ejection fraction (EF), and stroke volume (SV) decreased. These effects were reversed by the Cor treatment. Western blot analysis indicated p-AMPK levels were higher in the Model group than those in the Sham group. After Cor treatment, p-AMPK levels increased but later decreased after treatment with Dor. In addition, myocardial mitochondrial abnormalities were reduced and ATP levels increased in the Cor group compared with the Model group, which were reversed by Dor. Lastly, Cor was found to target AMPK pathway-related genes. Conclusion: Cor exerts protective effects on HF by activating AMPK to improve mitochondrial function.

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Cardiomyocyte survivin protein expression is associated with cell size and DNA content in the failing human heart and is reversibly regulated after ventricular unloading

Cited by 14 publications

References 20 publications

Insulin Protects Cardiac Myocytes from Doxorubicin Toxicity by Sp1-Mediated Transactivation of Survivin

Insulin Protects Cardiac Myocytes from Doxorubicin Toxicity by Sp1-Mediated Transactivation of Survivin

Advances in mechanical circulatory support: Year in review

Cornus officinalis Sieb. et Zucc. Alleviates Mitochondrial Abnormalities and Heart Failure through AMPK

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