Programmed cell death induced by ceramide.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Obeid, LM; Linardic, CM; Karolak, LA; Hannun, YA

Published Date

  • March 19, 1993

Published In

Volume / Issue

  • 259 / 5102

Start / End Page

  • 1769 - 1771

PubMed ID

  • 8456305

Pubmed Central ID

  • 8456305

International Standard Serial Number (ISSN)

  • 0036-8075

Digital Object Identifier (DOI)

  • 10.1126/science.8456305

Language

  • eng

Conference Location

  • United States