Bcl-xL Inhibits Cytochrome c Release but Not Mitochondrial Depolarization during the Activation of Multiple Death Pathways by Tumor Necrosis Factor-α

摘要: Cells can respond differently to anti-CD95 antibody treatment. Type I cells show strong activation of caspase-8 and directly activate caspase-3. II weakly must amplify their death signal through the mitochondria. These be rescued by Bcl-xL. Here we that tumor necrosis factor-α induces both pathways, which inhibited benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (Z-VAD-fmk) Bcl-xL in a cooperative fashion. Death induced presence Z-VAD-fmk was associated with partial inhibition caspase-8, whereas no effects on cytochrome c release, DEVDase activity, intranucleosomal DNA cleavage were observed. Thus, is likely weakening death-inducing signaling complex-mediated diverting pathway. cooperates blocking pathway at level release. Surprisingly, although able block cytochromec it unable mitochondrial depolarization, suggesting these are separate events. This suggests mitochondria occupy two places apoptotic signaling, as initiators apoptosis release cas well target for effector caspases.