Back to Search
Start Over
Inhibition of NFkappaB induces caspase-independent cell death in human T lymphocytes.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2001 Oct 05; Vol. 287 (4), pp. 895-9. - Publication Year :
- 2001
-
Abstract
- Nuclear factor kappaB (NFkappaB) regulates the expression of various genes essential for cell survival. Here we demonstrate that suppression of NFkappaB nuclear import with SN50 peptide carrying the nuclear localization sequence (NLS) of the NFkappaB p50 subunit induces apoptosis in human peripheral blood T lymphocytes (T-PBL), which can be blocked with the pan-caspase inhibitor Z-VAD.fmk. However, even when caspase function is blocked, the addition of SN50 induces irreversible cell loss due to the reduction in the mitochondrial transmembrane potential (DeltaPsim) followed by disruption of the cell membrane, hallmarks of necrosis. These observations demonstrate that although inhibition of NFkappaB nuclear translocation by SN50 peptide can induce caspase-dependent apoptosis in T-PBL, cell death may still proceed in the absence of functional caspase activity. The availability of downstream caspases appears to determine the mode of cell death in NFkappaB defective cells.<br /> (Copyright 2001 Academic Press.)
- Subjects :
- Active Transport, Cell Nucleus physiology
Amino Acid Chloromethyl Ketones pharmacology
Caspase Inhibitors
Caspases metabolism
Cell Nucleus metabolism
Cells, Cultured
Cysteine Proteinase Inhibitors pharmacology
DNA Fragmentation
Flow Cytometry
Humans
In Situ Nick-End Labeling
Membrane Potentials physiology
Mitochondria drug effects
Mitochondria metabolism
NF-kappa B antagonists & inhibitors
Peptides metabolism
Peptides pharmacology
T-Lymphocytes drug effects
Apoptosis physiology
NF-kappa B metabolism
T-Lymphocytes physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0006-291X
- Volume :
- 287
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 11573949
- Full Text :
- https://doi.org/10.1006/bbrc.2001.5678