Figure 7. Schematic diagram of NiCl₂-induced mitochondria- and Fas-mediated caspase-dependent apoptosis.

NiCl₂ increases the cyt-c, Smac and HtrA2 release from the mitochondria into the cytosol. Cyt-c cleaves and activates caspase-9, which in turn cleaves and activates downstream caspases, such as caspase-3, 6 and 7. Caspase-3, 6 and 7 cleave PARP, which then induces apoptosis. Concurrently, Smac and HtrA2 inhibit XIAP expression, also contributing to apoptosis. NiCl₂ also promotes Fas and Fas ligand interactions, leading to activation of caspase-8 and casapase-10. Activated caspase-8 and 10 can directly cleave and activate downstream effector proteases, such as caspase-3, 6 and 7, leading to apoptosis.