What about other caspases? Some investigators have reported that procaspase-
3 polypeptide levels are unchanged after NGF withdrawal, raising the
possibility that caspase-3 fails to play a role in this process.138,173 Other experiments,
however, have suggested a different picture. In particular, Stefanis and
co-workers have reported that NGF-deprived PC12 cells activate a caspase that
is capable of cleaving DEVD-aminofluorocouramin,170 a substrate that can be
cleaved by caspase-3 but not caspase-2.35 Immunoblotting and affinity labeling
experiments likewise have indicated that neurotrophin withdrawal-induced
apoptosis in mouse neurons and neuronal cell lines is accompanied by conversion
of procaspase-3 to the active enzyme.175,177 These results, which are
difficult to reconcile with earlier reports, clearly indicate activation of caspase-
3 during neutrophin withdrawal-induced apoptosis. Interestingly, the DEVDAFC
cleavage activity reportedly appears later than JNK activity, raising the
possibility that caspase-3 activation follows Jun synthesis.170