Tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-induced apoptosis is dependent on activation of cysteine and serine proteases

We examined the role of caspases and serine protease(s) in cell death induc ed by tumour necrosis factor-related apoptosis-inducing ligand (TRAIL). Aft er incubation of adenocarcinoma cells with TRAIL, caspase-3, -8 were activa ted and the cleavage of Bid induced the release of cytochrome c, from the m itochondria to the cytosol. Tetrapeptide inhibitors of caspase-1, -2, -3, a nd -8 suppressed DNA fragmentation and attenuated the release of cytochrome c, whereas inhibitors of caspase-5 did not. Interestingly, the general ser ine protease(s) inhibitor 4-(2-aminoethyl)benzylsulfonyl fluoride (AEBSF) r esulted in the arrest of apoptosis. However, the AEBSF did not prevent the release of mitochondrial cytochrome c during TRAIL-induced apoptosis. From these results, we postulate that serine protease(s) may be involved in post -mitochondrial apoptotic events, that lead to the activation of the initiat or, caspase-9. (C) 2001 Academic Press.