Mitochondrial cytochrome c release precedes transmembrane depolarisation and caspase-3 activation during ceramide-induced apoptosis of Jurkat T cells

Apoptosis. 2002 Oct;7(5):387-94. doi: 10.1023/a:1020034906200.


Whilst the role of ceramide, a second messenger of the sphingolipid family, in the initiation of receptor-mediated apoptosis is controversial, a growing body of evidence is emerging for a role of ceramide in the amplification of apoptosis via mitochondrial perturbations that culminate in the activation of execution caspases. Treatment of Jurkat T cells with the cell-permeable analog, C(2)-ceramide, resulted in the rapid onset of apoptosis as evidenced by Annexin V-FITC staining of externalised phosphatidylserine residues. Cells bearing this early apoptotic marker had a reduced mitochondrial transmembrane potential (Delta(Psi)m) that was preceded by the release of cytochrome c from mitochondria. Subsequent activation of caspase-3 provides the link between these ceramide-induced mitochondrial changes and execution caspases that ultimately result in the physical destruction of the cell. Collectively these results demonstrate that ceramide signalling results in caspase-mediated apoptosis via mitochondrial cytochrome c release and are further supportive of the role of ceramide in the amplification of apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Annexin A5 / metabolism
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Caspase 3
  • Caspases / metabolism*
  • Ceramides / metabolism*
  • Cytochrome c Group / metabolism*
  • Eukaryotic Cells / cytology
  • Eukaryotic Cells / drug effects
  • Eukaryotic Cells / metabolism*
  • Fluorescein-5-isothiocyanate
  • Humans
  • Intracellular Membranes / drug effects
  • Intracellular Membranes / metabolism*
  • Intracellular Membranes / ultrastructure
  • Jurkat Cells
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Mitochondria / ultrastructure
  • Phosphatidylserines / metabolism
  • Sphingosine / analogs & derivatives*
  • Sphingosine / pharmacology


  • Annexin A5
  • Ceramides
  • Cytochrome c Group
  • N-acetylsphingosine
  • Phosphatidylserines
  • CASP3 protein, human
  • Caspase 3
  • Caspases
  • Fluorescein-5-isothiocyanate
  • Sphingosine