ArticleInternational journal of molecular sciences2021
Long-Chain and Very Long-Chain Ceramides Mediate Doxorubicin-Induced Toxicity and Fibrosis.
Article in International journal of molecular sciences, 2021. 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, 18 citations in OpenAlex.
- Cardiac Lipid Metabolism: Cells, Metabolites, and Rhythms.Circulation research · 2026Review
- DKC1 promotes colorectal cancer progression and therapy resistance by dysregulating sphingolipid biosynthesis.Nature communications · 2026Article
- A Systemic Selective Modified mRNA Delivery Platform for Preventing Chemotherapy-Induced Cardiotoxicity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeted analysis of sphingolipids and cytokines in plasma of dairy cows after calving reveals distinct impacts of systemic inflammation, ketosis, and mastitis.Journal of animal science and biotechnology · 2026Article
- Metabolomic and inflammatory signatures in congenital hypothyroidism: a longitudinal analysis of levothyroxine response.Frontiers in endocrinology · 2026Article
- Targeting SIRT1 stability: arctiin ameliorates doxorubicin-induced cardiac injury by inhibiting SMURF2 binding and enhancing protective lipid metabolism.Frontiers in pharmacology · 2026Article
- Discovering a predictive metabolic signature of drug-induced structural cardiotoxicity in cardiac microtissues.Archives of toxicology · 2025Article
- Ceramide Synthase 2 Promotes Cardiac Very-Long-Chain Dihydroceramide Accumulation and Is Linked to Arrhythmias and Heart Failure in Humans.International journal of molecular sciences · 2025Article
- Inhibition of ceramide synthesis improves the outcome of ischemia/reperfusion injury in cardiomyocytes derived from human induced pluripotent stem cell.Stem cell research & therapy · 2025Article
- Developing an approach for evaluating the cardiotoxic potential of botanicals.Frontiers in toxicology · 2025Review
- Omega-3 supplementation attenuates doxorubicin-induced cardiotoxicity but is not related to the ceramide pathway.Food science & nutrition · 2024Article
- Ceramides: a potential cardiovascular biomarker in young adult childhood cancer survivors?European heart journal open · 2024Article
- Endoplasmic reticulum stress and mitochondrial dysfunction during aging: Role of sphingolipids.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2023Article
- Potential Drug Targets for Ceramide Metabolism in Cardiovascular Disease.Journal of cardiovascular development and disease · 2022Review
- Establishment of a platform for measuring mitochondrial oxygen consumption rate for cardiac mitochondrial toxicity.Toxicological research · 2022Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Doxorubicin (Dox) is a chemotherapeutic agent with cardiotoxicity associated with profibrotic effects. Dox increases ceramide levels with pro-inflammatory effects, cell death, and fibrosis. The purpose of our study was to identify the underlying ceramide signaling pathways. We aimed to characterize the downstream effects on cell survival, metabolism, and fibrosis. Human fibroblasts (hFSF) were treated with 0.7 µM of Dox or transgenically overexpressed ceramide synthase 2 (FLAG-CerS2). Furthermore, cells were pre-treated with MitoTempo (MT) (2 h, 20 µM) or Fumonisin B1 (FuB) (4 h, 100 µM). Protein expression was measured by Western blot or immunofluorescence (IF). Ceramide levels were determined with mass spectroscopy (MS). Visualizations were conducted using laser scanning microscopy (LSM) or electron microscopy. Mitochondrial activity was measured using seahorse analysis. Dox and CerS2 overexpression increased CerS2 protein expression. Coherently, ceramides were elevated with the highest peak for C24:0. Ceramide- induced mitochondrial ROS production was reduced with MT or FuB preincubation. Mitochondrial homeostasis was reduced and accompanied by reduced ATP production. Our data show that the increase in pro-inflammatory ceramides is an essential contributor to Dox side-effects. The accumulation of ceramides resulted in a lipotoxic shift and subsequently mitochondrial structural and functional damage, which was partially reversible following inhibition of ceramide synthesis.
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