title: Caspase-3/CPP32-like activity is not sufficient to mediate apoptosis in an IL-2 dependent T cell line.
abstract: CTLL cells undergo apoptosis when cultured in the absence of IL-2. The IL-1beta-converting-enzyme (ICE)/ caspase family has been implicated as an integral component of some forms of apoptosis. Numerous members of the caspase family have been identified, and it appears as if caspase-3/CPP32 plays a critical role. Previously we demonstrated that ICE/caspase-1 expression increases in CTLL cells during apoptosis; however, inhibition of ICE activity did not abrogate apoptotic death. The purpose of this report is to determine if other members of the caspase family are involved in T cell apoptosis induced by growth factor starvation. We show that cytosolic CPP32-like activity, as measured by the cleavage of DEVD-pNA and poly(ADP-ribose) polymerase (PARP), increases during apoptosis following growth factor deprivation. Cytosolic CPP32-like activity is inhibited in cells treated with the broad spectrum ICE family inhibitor boc-aspartyl(OMe)-fluoromethylketone (D-FMK) and by VAD-FMK and DEVD-FMK which have greater specificity for CPP32-like ICE homologs; however, only the broad spectrum ICE inhibitor D-FMK inhibited apoptosis. Our results suggest that apoptosis induced by growth factor deprivation involves the caspase family, but increased CPP32-like activity is not sufficient to mediate apoptosis induced by IL-2 starvation.
authors.affiliation: Department of Cell Biology, Parke-Davis Pharmaceutical Research Company, Division of Warner-Lambert, Ann Arbor, MI 48105, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Vasilakos
authors.forename: T
authors.initials: T
authors.lastname: Lynch
authors.forename: T
authors.initials: T
authors.lastname: Ghayur
authors.forename: D A
authors.initials: DA
authors.lastname: Giegel
authors.forename: M
authors.initials: M
authors.lastname: Santoro
authors.forename: B D
authors.initials: BD
authors.lastname: Shivers