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Bcl-2 antagonizes apoptotic cell death induced by two new ceramide analogues

Ceramides which arise in part from the breakdown of sphingomyelin comprise a class of antiproliferative lipids and have been implicated in the regulation of programmed cell death better known as apoptosis. In the present study, two new synthetic ceramide analogues, N-thioacetylsphingosine and FS-5,...

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Main Authors: Wieder, Thomas (Author) , Geilen, Christoph C (Author) , Kolter, Thomas (Author) , Sadeghlar, Farsaneh (Author) , Sandhoff, Konrad (Author) , Brossmer, Reinhard (Author) , Ihrig, Petra (Author) , Perry, David (Author) , Orfanos, Constantin E (Author) , Hannun, Yusuf A (Author)
Format: Article (Journal)
Language:English
Published: July 1997
In: FEBS letters
Year: 1997, Volume: 411, Issue: 2, Pages: 260-264
ISSN:1873-3468
DOI:10.1016/S0014-5793(97)00717-5
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/S0014-5793(97)00717-5
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0014579397007175
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Author Notes:Thomas Wieder, Christoph C. Geilen, Thomas Kolter, Farsaneh Sadeghlar, Konrad Sandhoff, Reinhard Brossmer, Petra Ihrig, David Perry, Constantin E. Orfanos, Yusuf A Hannun
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Summary:Ceramides which arise in part from the breakdown of sphingomyelin comprise a class of antiproliferative lipids and have been implicated in the regulation of programmed cell death better known as apoptosis. In the present study, two new synthetic ceramide analogues, N-thioacetylsphingosine and FS-5, were used in Molt4 cells to induce cell death. Besides their cytotoxic effects at concentrations ≥14 μM the data obtained clearly show that both analogues induced apoptosis at concentrations below this critical concentration as assessed by trypan blue exclusion and cleavage of the death substrate poly-(ADP-ribose) polymerase (PARP). Additional experiments in bcl-2-transfected Molt4 cells revealed that the apoptotic but not the lytic effects of the analogues were antagonized by the apoptosis inhibitor Bcl-2. Furthermore, neither N-thio-acetylsphingosine nor FS-5 induced PARP cleavage in bcl-2-transfected Molt4 cells indicating that the induction of apoptotic cell death by cell permeable ceramides is not due to unspecific disturbance of the cell membrane.
Item Description:Elektronische Reproduktion der Druck-Ausgabe 14. Dezember 2000
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Physical Description:Online Resource
ISSN:1873-3468
DOI:10.1016/S0014-5793(97)00717-5

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