Sphingosine 1-Phosphate Inhibits Activation of Caspases that Cleave Poly(ADP-ribose) Polymerase and Lamins during Fas- and Ceramide-mediated Apoptosis in Jurkat T Lymphocytes

Abstract

Ceramide, a sphingolipid generated by the hydrolysis of membrane-associated sphingomyelin, appears to play a role as a gauge of apoptosis. A further metabolite of ceramide, sphingosine 1-phosphate (SPP), prevents ceramide-mediated apoptosis, and it has been suggested that the balance between intracellular ceramide and SPP levels may determine the cell fate (

Activation of caspase-3-like proteases in apoptosis induced by sphingosine and other long-chain bases in Hep3B hepatoma cells

“…However, it should be noted that the signalling pathways activated by different sphingolipids may be different, and that many sphingolipid-related phenomena are expressed in a cell-type-dependent manner. For example, ceramide generated by the hydrolysis of membrane-associated sphingomyelin induces apoptosis in Jurkat lymphocytes, but sphingosine 1-phosphate, a metabolite of ceramide, prevents ceramide-triggered apoptosis in these cells [38]. Similarly, different outcomes may be found when the same sphingolipid is added into the culture medium of different cell lines.…”

Enhancement of radiosensitivity by combined ceramide and dimethylsphingosine treatment in lung cancer cells

“…On the basis of these findings, one can speculate that combining radiotherapy with the regulation of endogenous ceramide levels may have synergistic effects on selected tumors. Thus, modifications in the sphingomyelin/ceramide signaling pathway are expected to be a potential tool to increase the therapeutic efficiency of radiation treatment of tumors (Chmura et al, 1997;Edsall et al, 1997Edsall et al, , 1998Susin et al, 1997;Cuvillier et al, 1998;Kleuser et al, 1998;Kolesnick et al, 1998;Zhivotovsky et al, 1999). Many inhibitors of ceramide synthesis such as DL-PDMP (DL-threo-1-phenyl 2-decanoyl amino-3-morpholino-1-propanol․ HCl), B13, and imipramine have already been tried in humans and animals.…”

“…In addition, the treatment with exogenous short chain homologues of ceramide mimics endogenously generated ceramide and induces apoptosis. However, the mechanisms that convey activation signals to the enzymes responsible for ceramide production are poorly defined, and the pivotal executioner of ceramide to the apoptotic response still remains arguable (Chmura et al, 1997;Susin et al, 1997;Edsall et al, 1997Edsall et al, , 1998Cuvillier et al, 1998;Kleuser et al, 1998;Kolesnick et al, 1998).…”

Activation of p38 Mitogen-Activated Protein Kinase Is Required for Death Receptor–Independent Caspase-8 Activation and Cell Death in Response to Sphingosine

“…Ceramide is further metabolized by ceramidase to generate sphingosine during the early stages of apoptosis. Moreover, sphingosine itself is capable of triggering apoptosis when added exogenously to a variety of leukemic cells or solid cancer cell lines (4). These findings have led to the proposal that sphingosine plays a key role in apoptosis signaling.…”