Bcl-xLcan inhibit apoptosis in cells that have undergone Fas-induced protease activation
Open Access
- 15 April 1997
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 94 (8) , 3759-3764
- https://doi.org/10.1073/pnas.94.8.3759
Abstract
Programmed cell death or apoptosis provides an irreversible mechanism for the elimination of excess or damaged cells. Several recent studies have implicated the activation of the interleukin 1β-converting enzyme/Ced-3 (ICE/Ced-3) family of proteases as the “point of no return” in apoptotic cell death, while others have suggested that loss of mitochondrial membrane potential (ΔΨm) is the ultimate determinant of cell death. The temporal relationship of these two events during apoptosis and the role of Bcl-2 proteins in inhibiting these steps has not been defined. To examine these issues, control and Bcl-xL-transfected Jurkat T cells were treated with Fas antibodies in the presence and absence of the ICE protease inhibitor zVAD-FMK. ICE/Ced-3 protease activity was monitored by following the cleavage of poly(ADP-ribose) polymerase (PARP) and ΔΨmwas followed by rhodamine 123 fluorescence. Although Bcl-xLexpression did not block Fas-induced protease activation, it substantially inhibited the subsequent loss of ΔΨmand cell death in Fas-treated cells. In contrast, zVAD-FMK blocked PARP cleavage as well as loss of ΔΨmand cell death. Together these data demonstrate that Bcl-xLcan maintain cell viability by preventing the loss of mitochondrial membrane potential that occurs as a consequence of ICE/Ced-3 protease activation.Keywords
This publication has 34 references indexed in Scilit:
- Induction of Apoptotic Program in Cell-Free Extracts: Requirement for dATP and Cytochrome cPublished by Elsevier ,1996
- FLICE, A Novel FADD-Homologous ICE/CED-3–like Protease, Is Recruited to the CD95 (Fas/APO-1) Death-Inducing Signaling ComplexCell, 1996
- Involvement of MACH, a Novel MORT1/FADD-Interacting Protease, in Fas/APO-1- and TNF Receptor–Induced Cell DeathCell, 1996
- A License to KillCell, 1996
- The cell-death machineCurrent Biology, 1996
- Proteolysis and the biochemistry of life-or-death decisions.The Journal of Experimental Medicine, 1996
- Mitochondrial control of nuclear apoptosis.The Journal of Experimental Medicine, 1996
- Apoptosis: mitochondria resurrected?The Journal of Experimental Medicine, 1996
- A bcl-2 transgene expressed in hepatocytes protects mice from fulminant liver destruction but not from rapid death induced by anti-Fas antibody injection.The Journal of Experimental Medicine, 1996
- The mitochondrial permeability transitionBiochimica et Biophysica Acta (BBA) - Reviews on Biomembranes, 1995