Inhibition of NF kappa B induces caspase-independent cell death in human Tlymphocytes

Nuclear factor kappaB (NF kappaB) regulates the expression of various genes essential for cell survival. Here we demonstrate that suppression of NF ka ppaB nuclear import with SN50 peptide carrying the nuclear localization seq uence (NLS) of the NF kappaB p50 subunit induces apoptosis in human periphe ral 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 ad dition of SN50 induces irreversible cell loss due to the reduction in the m itochondrial transmembrane potential (Delta Psim) followed by disruption of the cell membrane, hallmarks of necrosis. These observations demonstrate t hat although inhibition of NF kappaB nuclear translocation by SN50 peptide can induce caspase-dependent apoptosis in T-PBL, cell death may still proce ed in the absence of functional caspase activity. The availability of downs tream caspases appears to determine the mode of cell death in NF kappaB def ective cells. (C) 2001 Academic Press.