Premium
Bcl‐2 antagonizes apoptotic cell death induced by two new ceramide analogues
Author(s) -
Wieder Thomas,
Geilen Christoph C,
Kolter Thomas,
Sadeghlar Farsaneh,
Sandhoff Konrad,
Brossmer Reinhard,
Ihrig Petra,
Perry David,
Orfanos Constantin E,
Hannun Yusuf A
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)00717-5
Subject(s) - apoptosis , ceramide , poly adp ribose polymerase , programmed cell death , microbiology and biotechnology , trypan blue , transfection , cytotoxic t cell , biology , sphingolipid , caspase , jurkat cells , cell , chemistry , cell culture , biochemistry , polymerase , t cell , in vitro , immunology , dna , genetics , immune system
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.