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

FEBS Letters - Tập 411 Số 2-3 - Trang 260-264 - 1997
Thomas Wieder1,2, Christoph C. Geilen1, Thomas Kolter3, Farsaneh Sadeghlar3, Konrad Sandhoff3, Reinhard Brossmer4, Petra Ihrig4, David K. Perry5, Constantin E. Orfanos1, Yusuf A. Hannun5
1Department of Dermatology, University Medical Center Benjamin Franklin, The Free University of Berlin, Hindenburgdamm 30, D-12200 Berlin, Germany
2Institute of Molecular Biology and Biochemistry, University Medical Center Benjamin Franklin, The Free University of Berlin, Berlin, Germany
3Institute of Organic Chemistry and Biochemistry, University of Bonn, Bonn, Germany
4Institute of Biochemistry, University of Heidelberg, Heidelberg, Germany
5Department of Medicine, University Medical Center, Duke University, Durham, NC, USA

Tóm tắt

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 Molt 4 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 Molt 4 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 Molt 4 cells indicating that the induction of apoptotic cell death by cell permeable ceramides is not due to unspecific disturbance of the cell membrane.

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FEBS Letters

Tập 411 Số 2-3

260-264

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