Cited by 1,794Sphingolipid Metabolism and SignalingCell death mechanisms and regulationNatural product bioactivities and synthesis

Programmed Cell Death Induced by Ceramide

Obeid, Lina M., Linardic, Corinne M., Karolak, Linda A., Hannun, Yusuf A.·1993·Science

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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Crossref · 10.1126/science.8456305

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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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