ArticleAmerican journal of physiology. Heart and circulatory physiology2019
Cardioprotective roles of sestrin 1 and sestrin 2 against doxorubicin cardiotoxicity.
Article in American journal of physiology. Heart and circulatory physiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- The Role of mTOR in the Doxorubicin-Induced Cardiotoxicity: A Systematic Review.Cell biochemistry and biophysics · 2025Pooled it
- Review
- Sestrins: a new therapeutic target for endothelial dysfunction and cardiovascular disease prevention.Annals of medicine · 2025Review
- Sestrin2 ameliorates LPS-induced cardiomyocyte injury by inhibiting ferroptosis via the Nrf2/HO-1 pathway.European journal of medical research · 2025Article
- Doxorubicin or Epirubicin Versus Liposomal Doxorubicin Therapy-Differences in Cardiotoxicity.Cardiovascular toxicology · 2025Review
- Restoration of Sestrin 3 Expression Mitigates Cardiac Oxidative Damage in Ischemia-Reperfusion Injury Model.Antioxidants (Basel, Switzerland) · 2025Article
- Levels of Sestrin-1 in Rheumatoid Arthritis Patients: Exploring the Association with Atherosclerosis.International journal of general medicine · 2025Article
- Mitophagy in Doxorubicin-Induced Cardiotoxicity: Insights into Molecular Biology and Novel Therapeutic Strategies.Biomolecules · 2024Review
- SESN2 attenuates sevoflurane-induced cognitive impairment and neuroinflammation in rats.Experimental brain research · 2024Article
- Role of sestrins in metabolic and aging-related diseases.Biogerontology · 2024Review
- Antioxidant genes in cancer and metabolic diseases: Focusing on Nrf2, Sestrin, and heme oxygenase 1.International journal of biological sciences · 2024Review
- The Essential Strategies to Mitigate Cardiotoxicity Caused by Doxorubicin.Life (Basel, Switzerland) · 2023Review
- Muscular Sestrins: Roles in Exercise Physiology and Stress Resistance.Biomolecules · 2023Review
- Article
- Cardiac SIRT1 ameliorates doxorubicin-induced cardiotoxicity by targeting sestrin 2.Redox biology · 2022Article
- The functions and roles of sestrins in regulating human diseases.Cellular & molecular biology letters · 2022Review
- Sarcopenia-derived exosomal micro-RNA 16-5p disturbs cardio-repair via a pro-apoptotic mechanism in myocardial infarction in mice.Scientific reports · 2021Article
- Sestrins regulate muscle stem cell metabolic homeostasis.Stem cell reports · 2021Article
- Sestrins in Physiological Stress Responses.Annual review of physiology · 2021Review
- TOR Signaling Pathway in Cardiac Aging and Heart Failure.Biomolecules · 2021Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Doxorubicin is a chemotherapy medication widely used to treat a variety of cancers. Even though it offers one of the most effective anti-cancer treatments, its clinical use is limited because of its strong cardiotoxicity that can lead to fatal conditions. Here, we show that sestrin 1 and sestrin 2, members of the sestrin family of proteins that are stress-inducible regulators of metabolism, are critical for suppressing doxorubicin cardiotoxicity and coordinating the AMPK-mammalian target of rapamycin complex 1 (mTORC1) autophagy signaling network for cardioprotection. Expression of both sestrin 1 and sestrin 2 was highly increased in the mouse heart after doxorubicin injection. Genetic ablation of sestrin 1 and sestrin 2 rendered mice more vulnerable to doxorubicin and exacerbated doxorubicin-induced cardiac pathologies including cardiomyocyte apoptosis and cardiac dysfunction. These pathologies were associated with strong dysregulation of the cardiac signaling network, including suppression of the AMPK pathway and activation of the mTORC1 pathway. Consistent with AMPK downregulation and mTORC1 upregulation, autophagic activity of heart tissue was diminished, leading to prominent accumulation of autophagy substrate, p62/SQSTM1. Taken together, our results indicate that sestrin 1 and sestrin 2 are important cardioprotective proteins that coordinate metabolic signaling pathways and autophagy to minimize cardiac damage in response to doxorubicin insult. Augmenting this protective mechanism could provide a novel therapeutic rationale for prevention and treatment of doxorubicin cardiotoxicity.
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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.