Apoptotic cell death occurs in the absence of caspase-3-like activity in PC12 cells and sympathetic neurons.A, PC12 cells were deprived of serum overnight in the presence or absence of the indicated concentrations of DEVD-FMK or zVAD-FMK. They were subsequently fixed and stained with Hoechst 33342 (1 μg/ml; Sigma). The arrows indicate apoptotic nuclei. B, Neuronally differentiated PC12 cells were deprived of NGF in the presence or absence of various concentrations of DEVD-FMK and assessed in parallel at 24 hr for caspase-3-like activity and survival. Survival is reported as the number of intact nuclei present at 24 hr relative to the number of nuclei present at time 0 after NGF deprivation and is given as mean ± SEM of three samples. C, Cultured rat sympathetic neurons were deprived of NGF in the presence or absence of zVAD-FMK (100 μm) or DEVD-FMK (100 μm), and survival was assessed 48 hr later. Sympathetic neurons treated with 100 ng/ml NGF were assessed in parallel. Survival is reported relative to that in the same cultures before NGF deprivation and is given as mean ± SEM of three samples.