Apoptosis induced by gamma irradiation in peripheral blood mononuclear cells is not mediated by cytochrome-c release and only partially involves caspase-3-like proteases.
Caspase 3 has been shown to be actively involved in the apoptotic process in thymocytes after gamma-irradiation. We examined caspase 3 activation in mature peripheral blood lymphocytes (PBL) after gamma irradiation. Since the activation of caspase 3 is generally prceded by a decrease in mitochondrial membrane potential (delta psi m) and cytochrome c release, these two parameters were also examined. Apoptosis in PBL after a 5-Gy gamma irradiation, is characterized by a decrease in delta psi m, but surprisingly no release of cytochrome-c and only a weak caspase 3 activation was noticed. In contrast, staurosporin treated PBL showed a decrease in delta psi m with cytochrome-c release and a clear caspase 3 activation. We were unable to block the decrease in delta psi m with the caspase-inhibitors zVAD-fmk or zDEVD-fmk after gamma irradiation, but DNA fragmentation as measured by the TUNEL assay was partially inhibited. Therefore, in gamma irradiated mature PBL, caspase-dependent and -independent pathways, but not cytochrome c, seem to be involved in the apoptotic process.
Louagie
H
H
Department of Clinical Chemistry, Microbiology and Immunology, Flanders Interuniversity Institute for Biotechnology and University of Gent, Belgium.
Schotte
P
P
Vral
A
A
Cornelissen
M
M
Thierens
H
H
Beyaert
R
R
De Ridder
L
L
Philippe
J
J
D017209:Apoptosis / Q000528:radiation effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D003574:Cytochrome c Group / Q000378:metabolism; D005720:Gamma Rays; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects; D015398:Signal Transduction / Q000528:radiation effects*
D003574:Cytochrome c Group; D053148:Caspase 3; D020169:Caspases