Involvement of specific caspases in motoneuron cell death in vivo and in vitro following trophic factor deprivation.

The caspases have been shown to be key components of programmed cell death (PCD) in various cell types, including neurons. Caspase-3 (CPP32) is the predominant caspase that appears to be involved in cell death in several systems. In embryonic motoneuron cultures, caspase-3 activity increases beginning at 20 h following deprivation of trophic support, as determined by the cleavage of its specific substrates. Inhibition of caspase-3 by peptide inhibitors prevents the PCD of motoneurons following trophic factor deprivation in vitro, as well as in vivo. We also investigated the cleavage of poly(ADP-ribose) polymerase (PARP) in motoneurons after trophic factor withdrawal. No PARP cleavage was detected in either viable or dying cells. These data suggest that some components of the cell death machinery such as the involvement of caspases may be conserved in different cell types undergoing PCD, whereas the activation and specific substrates of the caspases may differ from one cell type to another.