Caspase-dependent initiation of apoptosis and XXXX by the Fas receptor in lymphoid cells: onset of @entity39 is associated with delayed ceramide increase.

@entity522 @entity39 @entity8186 @entity12 @entity204
Engagement of the Fas receptor promotes apoptosis by activation of caspases. In addition, alterations in plasma membrane lipid orientation and intracellular ceramide levels are often observed. In A20 B-lymphoma cells, @entity12 -induced cell @entity204 and phosphatidylserine (PS) externalization were completely prevented by the generic caspase inhibitor z-VAD-fmk. By contrast, the @entity522 inhibitor Ac-DEVD-cho only partially restored cell viability and had no effect on surface exposure of PS. Flow cytometric analysis after @entity12 treatment identified two populations of dead cells. In one, @entity204 was dependent on @entity522 and paralleled by DNA fragmentation and cell shrinkage. In the second, @entity204 occurred in the absence of @entity522 activity and apoptotic features but was also blocked by zVAD-fmk. By morphological criteria these were identified as apoptotic and @entity39 cells, respectively. Using fluorescent substrates, @entity522 activity was detected only in the apoptotic cell population, whereas @entity8186 activity was detected in both. Both forms of @entity8186 -dependent cell @entity204 were also detected downstream of Fas in Jurkat T-cells, where Fas-dependent PS externalization and delayed ceramide production, which is similar to results shown here in A20 cells, have been reported. However, for Raji B-cells, lacking lipid scrambling and ceramide production in response to Fas activation, only apoptosis was detected. Short-chain C2- or C6-ceramides, but not the respective inactive dihydro compounds or treatment with bacterial sphingomyelinase, induced predominantly @entity39 rather than apoptotic cell @entity204 in A20 B-, Raji B- and Jurkat T-cells. Thus, delayed elevation of ceramide is proposed to promote @entity39 in those Fas-stimulated cells where @entity8186 activation was insufficient to trigger @entity522 -dependent apoptosis.
