Programmed Cell Death Induced by Ceramide

DOI Web Site 被引用文献85件
  • Lina M. Obeid
    Department of Medicine, Duke University Medical Center, Durham, NC 27710.
  • Corinne M. Linardic
    Department of Medicine, Duke University Medical Center, Durham, NC 27710.
  • Linda A. Karolak
    Department of Medicine, Duke University Medical Center, Durham, NC 27710.
  • Yusuf A. Hannun
    Department of Medicine, Duke University Medical Center, Durham, NC 27710.

書誌事項

公開日
1993-03-19
DOI
  • 10.1126/science.8456305
公開者
American Association for the Advancement of Science (AAAS)

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説明

<jats:p> 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 <jats:sub>2</jats:sub> -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 <jats:sub>2</jats:sub> -dihydroceramide was also ineffective, which suggests a critical role for the sphingolipid double bond. The effects of C <jats:sub>2</jats:sub> -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. </jats:p>

収録刊行物

  • Science

    Science 259 (5102), 1769-1771, 1993-03-19

    American Association for the Advancement of Science (AAAS)

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