Caspase activation precedes FTP opening in TNF-α-induced apoptosis in L929 cells

摘要

In this work, we studied the apoptotic pathway in murine fibrosarcoma cells L929 exposed to tumor necrosis factor a (TNF-α) DNA fragmentation, activation of caspases, cytochrome c release and poly (ADP-ribose) polymerase cleavage were demonstrated We showed that the proapoptotic proteins Bid and Bax as well as caspase 8 are involved in the initiation of this apoptotic pathway triggered by TNF-α. Indeed, inhibition of caspase 8 could prevent TNF-a-induced DNA fragmentation. Furthermore, Bid and Bax translocation into mitochondria were already evidenced after 6 h. In contrast, permeability transition pore inhibitors did not prevent the DNA fragmentation induced by TNF-α. In addition, these events were not associated with changes in the mitochondria l membrane potential nor with the loss of ATP, which only occurred after 16 h. Taken together, these results underline the fact that TNF-α is able to induce caspase-dependent apoptosis in L929 in the absence of permeability transition pore opening.