ArticlePloS one2012
Inhibition of doxorubicin-induced senescence by PPARδ activation agonists in cardiac muscle cells: cooperation between PPARδ and Bcl6.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed.
- Calorie restriction modulates the transcription of genes related to stress response and longevity in human muscle: The CALERIE study.Aging cell · 2023Trial
- Mitochondrial-Targeted SS-31 Attenuates the Doxorubicin-Induced Cardiomyoblast H9C2 Cell Senescence.Biology · 2026Article
- Macrophage derived VEGF regulates macrophage senescence to inhibit radiation-induced dermatitis.Journal of translational medicine · 2025Article
- Identification and verification of biomarkers associated with neutrophils in acute myocardial infarction: integrated analysis of bulk RNA-seq, expression quantitative trait loci, and mendelian randomization.Frontiers in molecular biosciences · 2025Article
- DEAD-box helicase 17 (DDX17) protects cardiac function by promoting mitochondrial homeostasis in heart failure.Signal transduction and targeted therapy · 2024Article
- Anthracycline Cardiotoxicity Induces Progressive Changes in Myocardial Metabolism and Mitochondrial Quality Control: Novel Therapeutic Target.JACC. CardioOncology · 2024Article
- Underlying Mechanisms and Treatment of Cellular Senescence-Induced Biological Barrier Interruption and Related Diseases.Aging and disease · 2024Review
- Recent Advances in the Mechanisms of Cell Death and Dysfunction in Doxorubicin Cardiotoxicity.Reviews in cardiovascular medicine · 2023Review
- An integrative review of nonobvious puzzles of cellular and molecular cardiooncology.Cellular & molecular biology letters · 2023Review
- Increased Intracellular Free Zinc Has Pleiotropic Effects on Doxorubicin-Induced Cytotoxicity in hiPCS-CMs Cells.International journal of molecular sciences · 2023Article
- Review
- Single-cell transcriptome of the mouse retinal pigment epithelium in response to a low-dose of doxorubicin.Communications biology · 2022Article
- The role of cellular senescence in cardiac disease: basic biology and clinical relevance.Nature reviews. Cardiology · 2022Review
- Understanding the Protective Role of Exosomes in Doxorubicin-Induced Cardiotoxicity.Oxidative medicine and cellular longevity · 2022Review
- Identification and validation of senescence-related genes in circulating endothelial cells of patients with acute myocardial infarction.Frontiers in cardiovascular medicine · 2022Article
- Comparison between trabectedin and doxorubicin in soft-tissue sarcomas: a systematic review and meta-analysis.Annals of translational medicine · 2021Article
- Molecular mechanisms and cardiovascular implications of cancer therapy-induced senescence.Pharmacology & therapeutics · 2021Review
- PPAR Beta/Delta and the Hallmarks of Cancer.Cells · 2020Review
- Bcl6 Suppresses Cardiac Fibroblast Activation and Function via Directly Binding to Smad4.Current medical science · 2019Article
- Bcl6 knockdown aggravates hypoxia injury in cardiomyocytes via the P38 pathway.Cell biology international · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Senescence and apoptosis are two distinct cellular programs that are activated in response to a variety of stresses. Low or high doses of the same stressor, i.e., the anticancer drug doxorubicin, may either induce apoptosis or senescence, respectively, in cardiac muscle cells. We have demonstrated that PPARδ, a ligand-activated transcriptional factor that controls lipid metabolism, insulin sensitivity and inflammation, is also involved in the doxorubicin-induced senescence program. This occurs through its interference with the transcriptional repressor protein B cell lymphoma-6 (Bcl6). Low doses of doxorubicin increase the expression of PPARδ that sequesters Bcl6, thus preventing it from exerting its anti-senescent effects. We also found that L-165041, a specific PPARδ activator, is highly effective in protecting cardiomyocytes from doxorubicin-induced senescence through a Bcl6 related mechanism. In fact, L-165041 increases Bcl6 expression via p38, JNK and Akt activation, and at the same time it induces the release of Bcl6 from PPARδ, thereby enabling Bcl6 to bind to its target genes. L-165041 also prevented apoptosis induced by higher doses of doxorubicin. However, while experiments performed with siRNA analysis techniques very clearly showed the weight of Bcl6 in the cellular senescence program, no role was found for Bcl6 in the anti-apoptotic effects of L-165041, thus confirming that senescence and apoptosis are two very distinct stress response cellular programs. This study increases our understanding of the molecular mechanism of anthracycline cardiotoxicity and suggests a potential role for PPARδ agonists as cardioprotective agents.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.