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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

✍ Scribed by H Louagie; P Schotte; A Vral; M Cornelissen; H Thierens; R Beyaert; L De Ridder; J Philippe


Publisher
Elsevier Science
Year
1999
Tongue
English
Weight
212 KB
Volume
23
Category
Article
ISSN
1065-6995

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✦ Synopsis


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.