ArticleAntioxidants (Basel, Switzerland)2022
Effects of Ferroptosis on the Metabolome in Cardiac Cells: The Role of Glutaminolysis.
Article in Antioxidants (Basel, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 30 citations in OpenAlex.
- Metabolic reprogramming in cardiac fibrosis: mechanisms, crosstalk, and therapeutic interventions.Frontiers in physiology · 2026Review
- Metabolic alterations and redox homeostasis in ferroptosis: emerging mechanisms and therapeutic implications.Archives of medical science : AMS · 2026Article
- Targeting ferroptosis: a novel pathway in oral, oropharyngeal, hypopharyngeal, and laryngeal cancers.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- The role of ferroptosis in acute kidney injury: mechanisms and potential therapeutic targets.Molecular and cellular biochemistry · 2025Review
- ExosomalJournal of Zhejiang University. Science. B · 2024Article
- Cellular ROS and Antioxidants: Physiological and Pathological Role.Antioxidants (Basel, Switzerland) · 2024Article
- Targeting Ferroptosis: A Novel Strategy for the Treatment of Atherosclerosis.Mini reviews in medicinal chemistry · 2024Review
- XJB-5-131 protects chondrocytes from ferroptosis to alleviate osteoarthritis progression via restoring Pebp1 expression.Journal of orthopaedic translation · 2024Article
- Synergistic interactions of cytarabine-adavosertib in leukemic cell lines proliferation and metabolomic endpoints.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Article
- Cardioprotective potential of mitochondria-targeted antioxidant, mito-TEMPO, in 5-fluorouracil-induced cardiotoxicity.Cancer chemotherapy and pharmacology · 2023Article
- Novel perspective in transplantation therapy of mesenchymal stem cells: targeting the ferroptosis pathway.Journal of Zhejiang University. Science. B · 2023Review
- The Effects of Amyloid-β on Metabolomic Profiles of Cardiomyocytes and Coronary Endothelial Cells.Journal of Alzheimer's disease : JAD · 2023Article
- Ferroptosis and mitochondrial dysfunction in acute central nervous system injury.Frontiers in cellular neuroscience · 2023Review
- Ferroptosis and its role in skeletal muscle diseases.Frontiers in molecular biosciences · 2022Review
- The underlying pathological mechanism of ferroptosis in the development of cardiovascular disease.Frontiers in cardiovascular medicine · 2022Review
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Ferroptosis is a novel iron-dependent regulated cell death mechanism that affects cell metabolism; however, a detailed metabolomic analysis of ferroptotic cells is not yet available. Here, we elucidated the metabolome of H9c2 cardioblasts by gas chromatography-mass spectrometry during ferroptosis induced by RSL3, a GPX4 inhibitor, in the presence of ferrostatin-1 (a ferroptosis inhibitor), XJB-5-131 (a mitochondrial-targeted ROS scavenger), or TSM-1005-44 (a newly developed cellular ROS scavenger). Results demonstrated that RSL3 decreased the levels of amino acids involved in glutathione synthesis more than two-fold. In contrast, saturated fatty acids levels were markedly increased in RSL3-challenged cells, with no effects on unsaturated fatty acids. RSL3 significantly altered the levels of mitochondrial tricarboxylic acid cycle intermediates; isocitrate and 2-oxoglutarate were found to increase, whereas succinate was significantly decreased in RSL3-challenged cells. Ferrostatin-1, XJB-5-131, and TSM-1005-44 prevented RSL3-induced cell death and conserved the metabolomic profile of the cells. Since 2-oxoglutarate is involved in the regulation of ferroptosis, particularly through glutamine metabolism, we further assessed the role of glutaminolysis in ferroptosis in H9c2 cardioblasts. Genetic silencing of GLS1, which encodes the K-type mitochondrial glutaminase (glutaminase C), protected against ferroptosis in the early stage. In conclusion, our study demonstrates that RSL3-induced ferroptosis impairs the metabolome of H9c2 cardioblasts.
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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.