ArticleThe Journal of experimental medicine2000
Overexpression of acid ceramidase protects from tumor necrosis factor-induced cell death.
Article in The Journal of experimental medicine, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 171 citations in OpenAlex.
- Curcumin as a ceramide metabolism-targeting agent: Molecular mechanisms and therapeutic implications in cancer.Molecular biology reports · 2026Review
- Ceramide metabolism alterations contribute to Tumor Necrosis Factor-induced melanoma dedifferentiation and predict resistance to immune checkpoint inhibitors in advanced melanoma patients.Frontiers in immunology · 2024Article
- Article
- Direct reprogramming induces vascular regeneration post muscle ischemic injury.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Inhibition of Lysosomal Function Mitigates Protective Mitophagy and Augments Ceramide Nanoliposome-Induced Cell Death in Head and Neck Squamous Cell Carcinoma.Molecular cancer therapeutics · 2020Article
- Receptor-interacting Ser/Thr kinase 1 (RIPK1) and myosin IIA-dependent ceramidosomes form membrane pores that mediate blebbing and necroptosis.The Journal of biological chemistry · 2019Article
- Novel Sphingolipid-Based Cancer Therapeutics in the Personalized Medicine Era.Advances in cancer research · 2018Review
- Comparison of a ceramidase inhibitor (ceranib-2) with C2 ceramide and cisplatin on cytotoxicity and apoptosis of glioma cells.Turkish journal of biology = Turk biyoloji dergisi · 2018Article
- Ceramide and Ischemia/Reperfusion Injury.Journal of lipids · 2018Review
- Acid ceramidase and its inhibitors: aOncotarget · 2017Article
- Augmented trophoblast cell death in preeclampsia can proceed via ceramide-mediated necroptosis.Cell death & disease · 2017Article
- Acid Sphingomyelinase Mediates Oxidized-LDL Induced Apoptosis in Macrophage via Endoplasmic Reticulum Stress.Journal of atherosclerosis and thrombosis · 2016Article
- Sphingosine-1-Phosphate (S1P) Impacts Presynaptic Functions by Regulating Synapsin I Localization in the Presynaptic Compartment.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- Deletions in the cytoplasmic domain of iRhom1 and iRhom2 promote shedding of the TNF receptor by the protease ADAM17.Science signaling · 2015Article
- Induction of apoptosis in prostate cancer cells by the novel ceramidase inhibitor ceranib-2.In vitro cellular & developmental biology. Animal · 2015Article
- Homoharringtonine, a clinically approved anti-leukemia drug, sensitizes tumor cells for TRAIL-induced necroptosis.Cell communication and signaling : CCS · 2015Article
- Article
- TNF-induced necroptosis and PARP-1-mediated necrosis represent distinct routes to programmed necrotic cell death.Cellular and molecular life sciences : CMLS · 2014Article
- Endogenous ceramide contributes to the transcytosis of oxLDL across endothelial cells and promotes its subendothelial retention in vascular wall.Oxidative medicine and cellular longevity · 2014Article
- The proteases HtrA2/Omi and UCH-L1 regulate TNF-induced necroptosis.Cell communication and signaling : CCS · 2013Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor necrosis factor (TNF) signals cell death and simultaneously induces generation of ceramide. To evaluate the contribution of ceramide to TNF-dependent cell death, we generated clones of the TNF-sensitive cell line L929 that constitutively overexpress human acid ceramidase (AC). Ceramidase, in concert with sphingosine kinase, metabolizes ceramide to sphingosine-1-phosphate (SPP), an inducer of proliferation. In response to TNF, parental L929 cells display a significant increase in intracellular ceramide correlated with an "atypical apoptosis" characterized by membrane blebbing, DNA fragmentation and degradation of poly(ADP-ribose) polymerase despite a lack of caspase activity. These features are strongly reduced or absent in AC-overexpressing cells. Pharmacological suppression of AC with N-oleoylethanolamine restored the accumulation of intracellular ceramide as well as the sensitivity of the transfectants to TNF, implying that an enhanced metabolization of intracellular ceramide by AC shifts the balance between intracellular ceramide and SPP levels towards cell survival. Correspondingly, inhibition of ceramide production by acid sphingomyelinase also increased survival of TNF-treated L929 cells.
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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.