Sphingolipid signalling: molecular basis and role in TNF-alpha-induced cell death

Expert Rev Mol Med. 2002 Dec 20;4(28):1-15. doi: 10.1017/S146239940200546X.


Various lipidic molecules serve as second messengers for transducing signals from the cell surface to the cell interior and trigger specific cellular responses. Sphingolipids represent a complex group of lipids that have recently emerged as new transducers in eukaryotic cells. Several sphingolipid molecules are able to modulate cell growth, differentiation and death. This review summarises current knowledge of the signalling functions of sphingolipids, especially in the regulation of tumour necrosis factor [alpha] (TNF-[alpha])-mediated cytotoxic effects. TNF-[alpha] is a multifaceted cytokine that controls a wide range of immune responses in mammals, including induction of programmed cell death (also called apoptosis). On the basis of recent observations, a working model is proposed for the molecular mechanisms underlying regulation of sphingolipid generation following TNF-[alpha] receptor 1 activation. The implications of these findings for the development of future pharmacological strategies to prevent the cytotoxic TNF-[alpha] response and subsequent cellular dysfunctions (as seen in various human diseases) are discussed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • Cell Death / drug effects
  • Cellular Structures / physiology
  • Humans
  • Models, Biological
  • Second Messenger Systems / physiology
  • Signal Transduction / drug effects
  • Signal Transduction / genetics*
  • Sphingolipids / metabolism
  • Sphingolipids / physiology*
  • Tumor Necrosis Factor-alpha / pharmacology*


  • Sphingolipids
  • Tumor Necrosis Factor-alpha