ArticleThe Journal of biological chemistry2015
Tumor Necrosis Factor-α (TNFα)-induced Ceramide Generation via Ceramide Synthases Regulates Loss of Focal Adhesion Kinase (FAK) and Programmed Cell Death.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 71 citations in OpenAlex.
- Sphingolipid Metabolism in Obesity: Bidirectional Regulation and Comparative Perspectives on Plant Sphingolipids.Nutrients · 2026Review
- Article
- Adipose tissue ceramides: emerging lipid components of extracellular vesicles and their influence on metabolic dysregulation.Frontiers in endocrinology · 2026Review
- Proinflammatory cytokines modify CaFrontiers in physiology · 2026Article
- Impact of Nutrition on Sphingolipid-Regulated Physiology: A Review.Molecular nutrition & food research · 2025Review
- Spatial regulation of mitochondrial membrane potential by α5β1 integrin engagement in collective cell migration.Journal of cell science · 2025Article
- Granulosa cell RNA-Seq insights into senescence and sphingolipid metabolism disorder in PCOS: aspirin as a potential therapeutic drug.Reproductive biology and endocrinology : RB&E · 2025Article
- Role of Canonical and Non-Canonical Sphingolipids and their Metabolic Enzymes in Bone Health.Current osteoporosis reports · 2025Review
- Machine learning approach in canine mammary tumour classification using rapid evaporative ionization mass spectrometry.Analytical and bioanalytical chemistry · 2025Article
- The vascular endothelium as decision maker in lung injury.Frontiers in cell and developmental biology · 2025Review
- Enzymes of sphingolipid metabolism as transducers of metabolic inputs.Biochemical Society transactions · 2024Review
- Sphingolipid-Induced Bone Regulation and Its Emerging Role in Dysfunction Due to Disease and Infection.International journal of molecular sciences · 2024Review
- GIMAP5 deficiency reveals a mammalian ceramide-driven longevity assurance pathway.Nature immunology · 2024Article
- Biological function, topology, and quantification of plasma membrane Ceramide.Advances in biological regulation · 2024Review
- Metabolic signatures of combined exercise and fasting: an expanded perspective on previous telomere length findings.Frontiers in aging · 2024Article
- Independent association of hypovitaminosis d with non-alcoholic fatty liver disease in people with chronic spinal cord injury: a cross-sectional study.Journal of endocrinological investigation · 2024Article
- Mitochondrial Lipid Metabolism Genes as Diagnostic and Prognostic Indicators in Hepatocellular Carcinoma.Current genomics · 2023Article
- The heat shock protein Hsp27 controls mitochondrial function by modulating ceramide generation.Cell reports · 2023Article
- Natural Products and Small Molecules Targeting Cellular Ceramide Metabolism to Enhance Apoptosis in Cancer Cells.Cancers · 2023Review
- Long- and very long-chain ceramides are predictors of acute kidney injury in patients with acute coronary syndrome: the PEACP study.Cardiovascular diabetology · 2023Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Ceramide synthases (CerS1-CerS6), which catalyze the N-acylation of the (dihydro)sphingosine backbone to produce (dihydro)ceramide in both the de novo and the salvage or recycling pathway of ceramide generation, have been implicated in the control of programmed cell death. However, the regulation of the de novo pathway compared with the salvage pathway is not fully understood. In the current study, we have found that late accumulation of multiple ceramide and dihydroceramide species in MCF-7 cells treated with TNFα occurred by up-regulation of both pathways of ceramide synthesis. Nevertheless, fumonisin B1 but not myriocin was able to protect from TNFα-induced cell death, suggesting that ceramide synthase activity is crucial for the progression of cell death and that the pool of ceramide involved derives from the salvage pathway rather than de novo biosynthesis. Furthermore, compared with control cells, TNFα-treated cells exhibited reduced focal adhesion kinase and subsequent plasma membrane permeabilization, which was blocked exclusively by fumonisin B1. In addition, exogenously added C6-ceramide mimicked the effects of TNFα that lead to cell death, which were inhibited by fumonisin B1. Knockdown of individual ceramide synthases identified CerS6 and its product C16-ceramide as the ceramide synthase isoform essential for the regulation of cell death. In summary, our data suggest a novel role for CerS6/C16-ceramide as an upstream effector of the loss of focal adhesion protein and plasma membrane permeabilization, via the activation of caspase-7, and identify the salvage pathway as the critical mechanism of ceramide generation that controls cell death.
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