Scw. Ko et al., Functional characterization of Jurkat T cells rescued from CD95/Fas-induced apoptosis through the inhibition of caspases, BIOC BIOP R, 270(3), 2000, pp. 1009-1015
Citations number
29
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
The caspases are known to play a pivotal role in the triggering and executi
on of apoptosis in virtually all cell types. Because inappropriate apoptosi
s is a prominent feature of many human diseases, the caspases are attractiv
e targets for therapeutic intervention, In the present study we investigate
d whether Jurkat T lymphocytes rescued from Fas-induced cell death through
the inhibition of caspases are functional. Here we show that the pan-caspas
e, tripeptide inhibitor, benzyloxycarbonyl-Val-Ala-Asp (Ome) fluoromethylke
tone (z-VAD-FMK), inhibited the activation of caspase-2, -3, -7, and -8, an
d subsequently apoptosis in Jurkat T lymphocytes induced by agonistic anti-
Fas, The apoptotic signals induced by the cross-linking of the Fas antigen
have a relatively long half-life, as z-VAD-FMK had to be continuously prese
nt in the culture medium for 72 h after Fas stimulation in order to maintai
n cell survival. After 72 h, the z-VAD-FMK-rescued cells proliferate normal
ly and responded to activation induced cell, death after phytohaemaglutinin
treatment, and readily undergo apoptosis when restimulated with agonistic
Fas antibodies. Taken together, our results demonstrate that Jurkat T cells
rescued from Fas-mediated cell death through the inhibition of caspases ar
e functional, (C) 2000 Academic Press.