Ceramide-induced apoptosis is mediated by caspase activation independently from retinoblastoma protein post-translational modification

Angelo Spinedi, Alessandra Amendola, Sabrina Di Bartolomeo, Mauro Piacentini

Research output: Contribution to journalArticlepeer-review

Abstract

Recent evidence suggests that untimely retinoblastoma protein (RB) dephosphorylation and/or proteolytic degradation might provide key events down-stream cysteine protease (caspase) activation in apoptosis induction. We have dealt with this issue by studying apoptosis induced by N-hexanoylsphingosine (C6-Cer) in CHP-100 human neuroepithelioma cells, maintained in complete growth medium. We report that C6-Cer-induced apoptosis occurred predominantly in G1/S phases of the cycle and was associated with RB dephosphorylation, in the setting of negligible Bcl-2 expression. Apoptosis was also associated with poly(ADP-ribose) polymerase (PARP) cleavage, thus indicating activation of CPP32/Yama/apopain (caspase-3); however, while the tripeptide caspase inhibitor Z-Val-Ala-DL-Asp-fluoromethhylketone was able to prevent both C6-Cer-induced PARP cleavage and apoptosis, it was ineffective in preventing RB dephosphorylation. Moreover proteolytic RB cleavage occurred only to a marginal extent after C6-Cer treatment. These results indicate that apoptosis induced by ceramide in CHP-100 cells is caspase-mediated, but RB post-translational modification does not provide a key step, downstream caspase activation, in apoptosis execution.

Original languageEnglish
Pages (from-to)852-857
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume243
Issue number3
DOIs
Publication statusPublished - Feb 24 1998

Keywords

  • Apoptosis
  • Caspase
  • Ceramide
  • Retinoblastoma protein

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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