APOPTOSIS INDUCED BY γ IRRADIATION IN PERIPHERAL BLOOD MONONUCLEAR CELLS IS NOT MEDIATED BY CYTOCHROME-C RELEASE AND ONLY PARTIALLY INVOLVES CASPASE-3-LIKE PROTEASES

Abstract

Caspase 3 has been shown to be actively involved in the apoptotic process in thymocytes after γ-irradiation. We examined caspase 3 activation in mature peripheral blood lymphocytes (PBL) after γ irradiation. Since the activation of caspase 3 is generally prceded by a decrease in mitochondrial membrane potential (ΔΨm) and cytochrome c release, these two parameters were also examined. Apoptosis in PBL after a 5-Gy γ irradiation, is characterized by a decrease in ΔΨm, 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 ΔΨm with cytochrome-c release and a clear caspase 3 activation. We were unable to block the decrease in ΔΨm with the caspase-inhibitors zVAD-fmk or zDEVD-fmk after γ irradiation, but DNA fragmentation as measured by the TUNEL assay was partially inhibited. Therefore, in γ irradiated mature PBL, caspase-dependent and -independent pathways, but not cytochrome c, seem to be involved in the apoptotic process.