ArticleCell death & disease2013
Altering the sphingolipid acyl chain composition prevents LPS/GLN-mediated hepatic failure in mice by disrupting TNFR1 internalization.
Article in Cell death & disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
- Genetic Crosstalk Between Type 1 Diabetes and Sjögren's Syndrome: A Systematic Exploration of Risk Genes and Common Pathways.Journal of cellular and molecular medicine · 2025Article
- Ceramide present in cholangiocarcinoma-derived extracellular vesicle induces a pro-inflammatory state in monocytes.Scientific reports · 2023Article
- Neuronal Ganglioside and Glycosphingolipid (GSL) Metabolism and Disease : Cascades of Secondary Metabolic Errors Can Generate Complex Pathologies (in LSDs).Advances in neurobiology · 2023Article
- Contribution of specific ceramides to obesity-associated metabolic diseases.Cellular and molecular life sciences : CMLS · 2022Review
- Sphingolipid changes in Parkinson L444P GBA mutation fibroblasts promote α-synuclein aggregation.Brain : a journal of neurology · 2022Article
- Dihydroceramide- and ceramide-profiling provides insights into human cardiometabolic disease etiology.Nature communications · 2022Observational
- Roles for ADAM17 in TNF-R1 Mediated Cell Death and Survival in Human U937 and Jurkat Cells.Cells · 2021Article
- Review
- Deletion or inhibition of SphK1 mitigates fulminant hepatic failure by suppressing TNFα-dependent inflammation and apoptosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Sphingolipid metabolism as a marker of hepatotoxicity in drug-induced liver injury.Prostaglandins & other lipid mediators · 2020Article
- Glycolipids: Linchpins in the Organization and Function of Membrane Microdomains.Frontiers in cell and developmental biology · 2020Review
- Palmitoylation is required for TNF-R1 signaling.Cell communication and signaling : CCS · 2019Article
- Role of ceramide synthase 2 in G-CSF signaling and G-CSF-R translocation into detergent-resistant membranes.Scientific reports · 2019Article
- Herpes simplex virus 1 ICP6 impedes TNF receptor 1-induced necrosome assembly during compartmentalization to detergent-resistant membrane vesicles.The Journal of biological chemistry · 2019Article
- ST6Gal-I sialyltransferase promotes tumor necrosis factor (TNF)-mediated cancer cell survival via sialylation of the TNF receptor 1 (TNFR1) death receptor.The Journal of biological chemistry · 2018Article
- Oxidative stress elicited by modifying the ceramide acyl chain length reduces the rate of clathrin-mediated endocytosis.Journal of cell science · 2017Article
- Critical Role for Very-Long Chain Sphingolipids in Invariant Natural Killer T Cell Development and Homeostasis.Frontiers in immunology · 2017Article
- Article
- Exacerbation of experimental autoimmune encephalomyelitis in ceramide synthase 6 knockout mice is associated with enhanced activation/migration of neutrophils.Immunology and cell biology · 2015Article
- Hepatic fatty acid uptake is regulated by the sphingolipid acyl chain length.Biochimica et biophysica acta · 2014Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The involvement of ceramide in death receptor-mediated apoptosis has been widely examined with most studies focusing on the role of ceramide generated from sphingomyelin hydrolysis. We now analyze the effect of the ceramide acyl chain length by studying tumor necrosis factor α receptor-1 (TNFR1)-mediated apoptosis in a ceramide synthase 2 (CerS2) null mouse, which cannot synthesize very-long acyl chain ceramides. CerS2 null mice were resistant to lipopolysaccharide/galactosamine-mediated fulminant hepatic failure even though TNFα secretion from macrophages was unaffected. Cultured hepatocytes were also insensitive to TNFα-mediated apoptosis. In addition, in both liver and in hepatocytes, caspase activities were not elevated, consistent with inhibition of TNFR1 pro-apoptotic signaling. In contrast, Fas receptor activation resulted in the death of CerS2 null mice. Caspase activation was blocked because of the inability of CerS2 null mice to internalize the TNFR1; whereas Fc-TNFα was internalized to a perinuclear region in hepatocytes from wild-type mice, no internalization was detected in CerS2 null mice. Our results indicate that altering the acyl chain composition of sphingolipids inhibits TNFR1 internalization and inhibits selective pro-apoptotic downstream signaling for apoptosis.
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