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  • Title: Ceramide and sphingosine rapidly induce apoptosis of murine mast cells supported by interleukin-3 and stem cell factor.
    Author: Itakura A, Tanaka A, Aioi A, Tonogaito H, Matsuda H.
    Journal: Exp Hematol; 2002 Mar; 30(3):272-8. PubMed ID: 11882365.
    Abstract:
    OBJECTIVE: Ceramide and sphingosine, generated by sphingomyelinase-mediated hydrolysis of sphingomyelin, which packs tightly in the bilayer of the plasma membrane, have been proposed as intracellular mediators of apoptotic signals. However, precise function of endogenous sphingomyelin-cycle metabolites in mast cells has been unclear. Thus, we sought to define the involvement of ceramide and sphingosine in apoptotic pathways of mast cells. MATERIALS AND METHODS: We examined the effect of cell-permeable C(2)-ceramide, sphingosine, and sphingomyelinase on survival of murine bone marrow-derived cultured mast cells (BMCMC) supported by recombinant interleukin-3 (rIL-3) and/or recombinant stem cell factor (rSCF). Downstream signaling pathways of C(2)-ceramide and sphingosine were analyzed by using caspase inhibitors. RESULTS: C(2)-ceramide, sphingosine, and sphingomyelinase induced apoptosis in BMCMC in the presence of rIL-3 and/or rSCF, and Z-VAD-fmk (a broad caspase inhibitor), Z-DEVD-fmk (a caspase 3 inhibitor), and Z-IETD-fmk (a caspase 8 inhibitor) partially prevented apoptosis of BMCMC induced by C(2)-ceramide but not sphingosine. CONCLUSION: The present results suggest that ceramide and sphingosine may function as intracellular mediators of apoptotic signals in mast cells, which override survival signals from IL-3 and SCF. In addition, caspases may be partially involved in ceramide- but not sphingosine-mediated apoptosis of mast cells.
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