Programmed Cell Death Induced by Ceramide
Abstract
Sphingomyelin hydrolysis and ceramide generation have been implicated in a signal transduction pathway that mediates the effects of tumor necrosis factor-α (TNF-α) and other agents on cell growth and differentiation. In many leukemic cells, TNF-α causes DNA fragmentation, which leads to programmed cell death (apoptosis). C 2 -ceramide (0.6 to 5 μM), a synthetic cell-permeable ceramide analog, induced internucleosomal DNA fragmentation, which was inhibited by zinc ion. Other amphiphilic lipids failed to induce apoptosis. The closely related C 2 -dihydroceramide was also ineffective, which suggests a critical role for the sphingolipid double bond. The effects of C 2 -ceramide on DNA fragmentation were prevented by the protein kinase C activator phorbol 12-myristate 13-acetate, which suggests the existence of two opposing intracellular pathways in the regulation of apoptosis.
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Apoptosis can be activated by ceramide, and p53 appears to directly upregulate the ceramide synthase-encoding genes CERS5 and CERS6 and to induce ceramide production.
“Apoptosis also can be activated by ceramide,186 and p53 appears to directly upregulate the ceramide synthase-encoding genes CERS5 (Table 1) and CERS6187 and to induce ceramide production.188”
From Census and evaluation of p53 target genes (2017) · cites this paper as [186]
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- Authors
- Obeid, L. M., Linardic, C. M., Karolak, L. A., & Hannun, Y. A.
- Affiliations
- Duke Medical Center (US)
- Venue
- Science
- Published
- 1993-03-19
- Volume
- 259
- Issue
- 5102
- Pages
- 1769-1771
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2017729786
- Cited by
- 1,794
- References
- 28
- Citations by year
- 2026: 17 · 2025: 35 · 2024: 38 · 2023: 37 · 2022: 52 · 2021: 38 · 2020: 40 · 2019: 36 · 2018: 41 · 2017: 31 · 2016: 35 · 2015: 53 · 2014: 29 · 2013: 32 · 2012: 30
- FWCI
- 35.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Natural product bioactivities and synthesis
- Keywords
- ceramide, apoptosis, programmed cell death, C2-ceramide, sphingomyelin hydrolysis, sphingolipids, DNA fragmentation, zinc, dihydroceramide, protein kinase C, phorbol myristate acetate, leukemia cells, TNF signaling
- MeSH terms
- Ceramides, DNA, DNA Damage, Leukemia, Nucleosomes, Protein Kinase C, Sphingomyelins, Tetradecanoylphorbol Acetate, Tumor Cells, Cultured, Tumor Necrosis Factor-alpha, Zinc, Apoptosis
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