ArticlePloS one2015
Insulin Protects Cardiac Myocytes from Doxorubicin Toxicity by Sp1-Mediated Transactivation of Survivin.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It carries an expression of concern. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 50 citations in OpenAlex.
- Evaluation of the effects of diosmin in cyclophosphamide-induced nephrotoxicity: an experimental animal study.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Insulin Signalling-Inducible IFITM1 Promotes Multiple Myeloma Progression and Bortezomib Resistance.Journal of cellular and molecular medicine · 2026Article
- Circular RNAs: a small piece in the heart failure puzzle.Functional & integrative genomics · 2024Review
- A prospective randomized controlled trial to determine the safety and efficacy of extracorporeal shock waves therapy for primary prevention of subclinical cardiotoxicity in breast cancer patients without a cardiovascular risk treated with doxorubicin.Frontiers in cardiovascular medicine · 2024Article
- Micro-Executor of Natural Products in Metabolic Diseases.Molecules (Basel, Switzerland) · 2023Review
- Intermediate Molecular Phenotypes to Identify Genetic Markers of Anthracycline-Induced Cardiotoxicity Risk.Cells · 2023Article
- Nrf2: a dark horse in doxorubicin-induced cardiotoxicity.Cell death discovery · 2023Review
- Intermediate molecular phenotypes to identify genetic markers of anthracycline-induced cardiotoxicity risk.bioRxiv : the preprint server for biology · 2023Article
- Expression of Concern: Insulin Protects Cardiac Myocytes from Doxorubicin Toxicity by Sp1-Mediated Transactivation of Survivin.PloS one · 2023Article
- Cardiac Expression of Esophageal Cancer-Related Gene-4 is Regulated by Sp1 and is a Potential Early Target of Doxorubicin-Induced Cardiotoxicity.Cardiovascular toxicology · 2022Article
- Cardiomyocyte Atrophy, an Underestimated Contributor in Doxorubicin-Induced Cardiotoxicity.Frontiers in cardiovascular medicine · 2022Review
- Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Protect Cardiomyocytes from Doxorubicin-Induced Cardiomyopathy by Upregulating Survivin Expression via the miR-199a-3p-Akt-Sp1/p53 Signaling Pathway.International journal of molecular sciences · 2021Article
- Curcumin suppresses doxorubicin-induced cardiomyocyte pyroptosis via a PI3K/Akt/mTOR-dependent manner.Cardiovascular diagnosis and therapy · 2020Article
- Edaravone and Acetovanillone Upregulate Nrf2 and PI3K/Akt/mTOR Signaling and Prevent Cyclophosphamide Cardiotoxicity in Rats.Drug design, development and therapy · 2020Article
- Extracorporeal shock waves protect cardiomyocytes from doxorubicin-induced cardiomyopathy by upregulating survivin via the integrin-ILK-Akt-Sp1/p53 axis.Scientific reports · 2019Article
- Mechanistic interpretation of non-coding variants for discovering transcriptional regulators of drug response.BMC biology · 2019Article
- Simvastatin Inhibits Endotoxin-Induced Apoptosis in Liver and Spleen Through Up-Regulation of Survivin/NF-κB/p65 Expression.Frontiers in pharmacology · 2019Article
- Insulin down-regulates cardioprotective SUR2A in the heart-derived H9c2 cells: A possible explanation for some adverse effects of insulin therapy.Biochemistry and biophysics reports · 2018Article
- Study on Cardiotoxicity and Mechanism of "Fuzi" Extracts Based on Metabonomics.International journal of molecular sciences · 2018Article
- Simvastatin Protects Cardiomyocytes Against Endotoxin-induced Apoptosis and Up-regulates Survivin/NF-κB/p65 Expression.Scientific reports · 2018Article
Corrections and comments
- Expression of concern
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.