L. Stefanis et al., INDUCTION OF CPP32-LIKE ACTIVITY IN PC12 CELLS BY WITHDRAWAL OF TROPHIC SUPPORT - DISSOCIATION FROM APOPTOSIS, The Journal of biological chemistry, 271(48), 1996, pp. 30663-30671
Inhibitors of interleukin-1 beta converting enzyme (ICE) and a related
group of cysteine aspartases of the ICE/ced-3 family inhibit cell dea
th in a variety of settings, including in PC12 cells and sympathetic n
eurons following withdrawal of trophic support. To assess the particul
ar member(s) of the ICE/ced-3 family that are relevant to cell death a
nd to position their activation within the apoptotic pathway, we have
used specific substrates to measure ICE-like and CPP32-like enzymatic
activity in naive and neuronally differentiated PC12 cells that had be
en deprived of trophic support (nerve growth factor and/or serum). Rap
id induction of CPP32-like, but not ICE-like, activity was observed. c
-Jun kinase activation and the action of bcl-2 and other survival agen
ts, such as cell cycle blockers, a NO generator, N-acetylcysteine, aur
intricarboxylic acid, and actinomycin D occurred at a point further up
stream in the apoptotic pathway compared with the aspartase activation
. In living cells, zVAD-FRIR, a pseudosubstrate aspartase inhibitor, b
locked the activity/activation of the aspartase at concentrations abou
t one order of magnitude lower than those required to promote survival
, raising the possibility that the CPP32-like aspartase is not the mai
n death effector in this model.