| In these studies, we investigated the PARP cleavage during TransformingGrowth Factor-β1 (TGF-β1)-induced hepatocyte apoptosis and itsrelationship with caspase activation. In addition, we also investigated theceramide-induced apoptosis and its potential mechanism in A-431 cells.1,We reported for the first time that TGF-β1-induced caspase-dependentapoptosis is associated with caspase-independent PARP cleavage.Apoptosis has been shown to be a cell suicide program that is dependent onthe activation of caspase family of proteases in most, if not all, cases. PARPcleavage is always a concomitant event with apoptosis and has beenregarded as one of the most important hallmarks of caspase activation andapoptosis. We showed that TGF-β1-induced apoptosis is dependent on theactivation of caspase. However, caspase inhibition cannot inhibit theapoptosis-associated PARP cleavage. The results indicate that PARPcleavage may occur as an independent event that can be disassociated withcell apoptosis. In addition, our results suggest that TGF-β1-inducedcaspase-independent PARP cleavage requires the TGF-β1-induced synthesisof new proteins.2,We found ceramide-induced apoptotic cell death in A-431 cells involvesboth caspase-dependent and caspase-independent signaling. In relativelyearly stage of ceramide treatment, caspase-independent apoptosisrepresents the major form of cell death, and p38 MAP kinase plays a pivotalrole in this process. Incubation of cells with ceramide for long time results insubstantial cell death, which is associated with both typical and atypicalapoptotic characteristics. Furthermore, the apoptotic cell death in late stage ofceramide treatment is accompanied with the reduction of proportion of Sphase, suggesting a potential role of cell cycle-related signaling events in theprogression of apoptosis.
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