Programmed cell death induced by ceramide.
Sphingomyelin hydrolysis and ceramide generation have been implicated in a signal transduction pathway that mediates the effects of tumor necrosis factor-alpha (TNF-alpha) and other agents on cell growth and differentiation. In many leukemic cells, TNF-alpha causes DNA fragmentation, which leads to programmed cell death (apoptosis). C2-ceramide (0.6 to 5 microM), 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 C2-dihydroceramide was also ineffective, which suggests a critical role for the sphingolipid double bond. The effects of C2-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.
Duke Scholars
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- Zinc
- Tumor Necrosis Factor-alpha
- Tumor Cells, Cultured
- Tetradecanoylphorbol Acetate
- Sphingomyelins
- Protein Kinase C
- Nucleosomes
- Leukemia
- General Science & Technology
- DNA Damage
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Zinc
- Tumor Necrosis Factor-alpha
- Tumor Cells, Cultured
- Tetradecanoylphorbol Acetate
- Sphingomyelins
- Protein Kinase C
- Nucleosomes
- Leukemia
- General Science & Technology
- DNA Damage