The acid sphingomyelinase/ceramide pathway: Biomedical significance and mechanisms of regulation

Y. H. Zeidan, Y. A. Hannun

Research output: Contribution to journalArticle

81 Scopus citations

Abstract

One of the most intriguing enzymes of sphingolipid biology is acid sphingomyelinase (ASMase). In a phospholipase C reaction, ASMase catalyzes the cleavage of the phosphocholine head group of sphingomyelin to generate ceramide. Cumulative efforts of various laboratories over the past 40 years have placed ASMase and its product ceramide at the forefront of lipid research. Activation of the ASMase/ceramide pathway is a shared response to an ever-growing list of receptor and non-receptor mediated forms of cellular stress including: death ligands (TNFα, TRAIL, Fas ligand), cytokines (IL-1, IFNγ), radiation, pathogenic infections, cytotoxic agents and others. The strategic role of ASMase in lipid metabolism and cellular stress response has sparked interest in investigatig the molecular mechanisms underlying ASMase activation. In this article, we review the translational role of the ASMase/ceramide pathway and recent advances on its mechanisms of regulation.

Original languageEnglish (US)
Pages (from-to)454-466
Number of pages13
JournalCurrent Molecular Medicine
Volume10
Issue number5
DOIs
StatePublished - Jul 23 2010

Keywords

  • Apoptosis
  • Cancer
  • Ceramide
  • Membranes and sphingolipid
  • Protein kinase c
  • Sphingomyelinase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology

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