ArticleThe Journal of biological chemistry2010
Transcription factor GATA4 inhibits doxorubicin-induced autophagy and cardiomyocyte death.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 papers.
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Who cites it
149 citing papers in PubMed, 281 citations in OpenAlex.
- Development and Validation of a Diagnostic Nomogram to Predict the Anthracycline-Induced Early Cardiotoxicity in Children with Hematological Tumors.Cardiovascular toxicology · 2022Trial
- Transcriptional and epigenetic regulation of autophagy: mechanisms, disease relevance and therapeutic opportunities.Signal transduction and targeted therapy · 2026Review
- Effects of high-intensity aerobic exercise during multiple cycles of doxorubicin treatment on cardiac catabolism.Physical activity and nutrition · 2026Article
- Anti-PD-1 immune checkpoint inhibitor-induced cardiotoxicity is associated with dysfunctional metabolism, muscle wasting and autophagy.Scientific reports · 2026Article
- Article
- AICAr Inhibition of cardiomyocyte autophagy promotes p62-dependent NRF2 expression and protection against doxorubicin toxicity.Cellular and molecular life sciences : CMLS · 2025Article
- Ginsenoside Rb1 ameliorates post-doxorubicin treatment myocardial hypertrophy via CaN/NFATc4/GATA4.Journal of ginseng research · 2025Article
- Astaxanthin mitigates cardiac toxicity induced via doxorubicin by alleviating mitochondrial fission and autophagy in rats.Scientific reports · 2025Article
- Mir‑429 and GATA4 May Participate in Cerebral Ischemic Stroke by Regulating Autophagy and Apoptosis: the Impact of Chlorogenic Acid.Archives of Razi Institute · 2025Article
- Non-Coding RNAs in the Regulation of Doxorubicin-Induced Cardiotoxicity.Biomolecules · 2025Review
- DNA-damage-associated protein co-expression network in cardiomyocytes informs on tolerance to genetic variation and disease.iScience · 2025Article
- Natural products targeting regulated cell deaths for adriamycin-induced cardiotoxicity.Cell death discovery · 2025Review
- Cardiomyopathies and a brief insight into DOX-induced cardiomyopathy.The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology · 2025Review
- The role of GATA4 in mesenchymal stem cell senescence: A new frontier in regenerative medicine.Regenerative therapy · 2025Review
- Article
- Small Molecules Targeting Mitochondria: A Mechanistic Approach to Combating Doxorubicin-Induced Cardiotoxicity.Cardiovascular toxicology · 2025Review
- L-lysine Increases the Anticancer Effect of Doxorubicin in Breast Cancer by Inducing ROS-dependent Autophagy.Current cancer drug targets · 2025Article
- Doxorubicin induces cardiotoxicity by enhancing autophagy via mTOR signaling in hiPSC- and hESC-derived cardiomyocytes.Frontiers in cell and developmental biology · 2025Article
- Trace elements and metal nanoparticles: mechanistic approaches to mitigating chemotherapy-induced toxicity-a review of literature evidence.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2024Review
- Review
89 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Doxorubicin (DOX) is a potent anti-tumor drug known to cause heart failure. The transcription factor GATA4 antagonizes DOX-induced cardiotoxicity. However, the protective mechanism remains obscure. Autophagy is the primary cellular pathway for lysosomal degradation of long-lived proteins and organelles, and its activation could be either protective or detrimental depending on specific pathophysiological conditions. Here we investigated the ability of GATA4 to inhibit autophagy as a potential mechanism underlying its protection against DOX toxicity in cultured neonatal rat cardiomyocytes. DOX markedly increased autophagic flux in cardiomyocytes as indicated by the difference in protein levels of LC3-II (microtubule-associated protein light chain 3 form 2) or numbers of autophagic vacuoles in the absence and presence of the lysosomal inhibitor bafilomycin A1. DOX-induced cardiomyocyte death determined by multiple assays was aggravated by a drug or genetic approach that activates autophagy, but it was attenuated by manipulations that inhibit autophagy, suggesting that autophagy contributes to DOX cardiotoxicity. DOX treatment depleted GATA4 protein levels, which predisposed cardiomyocytes to DOX toxicity. Indeed, GATA4 gene silencing triggered autophagy that rendered DOX more toxic, whereas GATA4 overexpression inhibited DOX-induced autophagy, reducing cardiomyocyte death. Mechanistically, GATA4 up-regulated gene expression of the survival factor Bcl2 and suppressed DOX-induced activation of autophagy-related genes, which may likely be responsible for the anti-apoptotic and anti-autophagic effects of GATA4. Together, these findings suggest that activation of autophagy mediates DOX cardiotoxicity, and preservation of GATA4 attenuates DOX cardiotoxicity by inhibiting autophagy through modulation of the expression of Bcl2 and autophagy-related genes.
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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.