Recent evidence suggests that untimely retinoblastoma protein (RE) dephosphorylation and/or proteolytic degradation might provide key events downstream cysteine protease (caspase) activation in apoptosis induction. We have dealt with this issue by studying apoptosis induced by N-hexanoylsphingosine (C-6-Cer) in CHP-100 human neuroepithelioma cells, maintained in complete growth medium. We report that C-6-Cer-induced apoptosis occurred predominantly in G(1)/S phases of the cycle and was associated with RE 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 C-6-Cer-induced PARP cleavage and apoptosis, it was ineffective in preventing RE dephosphorylation. Moreover proteolytic RE cleavage occurred only to a marginal extent after C-6-Cer treatment. These results indicate that apoptosis induced by ceramide in CHP-100 cells is caspase-mediated, but RE post-translational modification does not provide a key step, downstream caspase activation, in apoptosis execution. (C) 1998 Academic Press.
Spinedi, A., Amendola, A., DI BARTOLOMEO, S., Piacentini, M. (1998). Ceramide-induced apoptosis is mediated by caspase activation independently from retinoblastoma protein post-translational modification. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 243(3), 852-857 [10.1006/bbrc.1998.8184].
Ceramide-induced apoptosis is mediated by caspase activation independently from retinoblastoma protein post-translational modification
SPINEDI, ANGELO;DI BARTOLOMEO, SABRINA;PIACENTINI, MAURO
1998-01-01
Abstract
Recent evidence suggests that untimely retinoblastoma protein (RE) dephosphorylation and/or proteolytic degradation might provide key events downstream cysteine protease (caspase) activation in apoptosis induction. We have dealt with this issue by studying apoptosis induced by N-hexanoylsphingosine (C-6-Cer) in CHP-100 human neuroepithelioma cells, maintained in complete growth medium. We report that C-6-Cer-induced apoptosis occurred predominantly in G(1)/S phases of the cycle and was associated with RE 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 C-6-Cer-induced PARP cleavage and apoptosis, it was ineffective in preventing RE dephosphorylation. Moreover proteolytic RE cleavage occurred only to a marginal extent after C-6-Cer treatment. These results indicate that apoptosis induced by ceramide in CHP-100 cells is caspase-mediated, but RE post-translational modification does not provide a key step, downstream caspase activation, in apoptosis execution. (C) 1998 Academic Press.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
