title: Inhibition of ceramide-induced apoptosis by Bcl-2.
abstract: Ceramide, a long chain sphingolipid that is generated intracellularly upon hydrolysis of membrane-associated sphingomyelin, has recently been implicated as a second messenger-like molecule that is produced distal to ligation of the tumour necrosis factor receptor type 1 (TNFR1), as well as the related Fas (CD95/Apo-1) molecule. It is well established that ligation of TNFR1 or Fas leads to apoptosis in most cases. Furthermore, it has also recently been demonstrated that exposure to cell-permeable synthetic ceramides can result in apoptosis in many cases. These and other observations have led to the hypothesis that accumulation of intracellular ceramide may be a common element of several pathways that result in apoptosis. Here we show that exposure to synthetic ceramides triggers apoptosis in the human T lymphoblastoid cell lines, CEM and Jurkat, and that overexpression of the apoptosis-repressor protein, Bcl-2, renders these cells resistant to the apoptosis-inducing effects of ceramide, as well as to several other stimuli. Since exposure to ceramides can result in either cell proliferation, differentiation, cycle arrest, or death, the level of Bcl-2 expression in a cell may be an important factor in determining the outcome of signals that result in intracellular generation of this sphingolipid.
authors.affiliation: La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Martin
authors.forename: S
authors.initials: S
authors.lastname: Takayama
authors.forename: A J
authors.initials: AJ
authors.lastname: McGahon
authors.forename: T
authors.initials: T
authors.lastname: Miyashita
authors.forename: J
authors.initials: J
authors.lastname: Corbeil
authors.forename: R N
authors.initials: RN
authors.lastname: Kolesnick
authors.forename: J C
authors.initials: JC
authors.lastname: Reed
authors.forename: D R
authors.initials: DR
authors.lastname: Green