P2X7 receptor-dependent and -independent T cell death is induced by nicotinamide adenine dinucleotide.
Adenosine-Diphosphate-Ribose, Animals, Apoptosis, Cell-Death, Cell-Proliferation, Cells-Cultured, Comparative-Study, Growth-Inhibitors, Mice-Inbred-BALB-C, Mice-Inbred-C57BL, Mice-Inbred-NOD, Mice-Knockout, NAD, Receptors-Purinergic-P2, Signal-Transduction, Substrate-Specificity, T-Lymphocytes, Time-Factors
J Immunol 2005 Feb; 174(4):1971-9.
Adding NAD to murine T lymphocytes inhibits their functions and induces annexin V binding. This report shows that NAD induces cell death in a subset of T cells within seconds whereas others do not die until many hours later. Low NAD concentrations (<10 microM) suffice to trigger rapid cell death, which is associated with annexin V binding and membrane pore formation, is not blocked by the caspase inhibitor Z-VADfmk, and requires functional P2X7 receptors. The slower induction of death requires higher NAD concentrations (>100 microM), is blocked by caspase inhibitor Z-VADfmk, is associated with DNA fragmentation, and does not require P2X7 receptors. T cells degrade NAD to ADP-ribose (ADPR), and adding ADPR to T cells leads to slow but not rapid cell death. NAD but not ADPR provides the substrate for ADP-ribosyltransferase (ART-2)-mediated attachment of ADP-ribosyl groups to cell surface proteins; expression of ART-2 is required for NAD to trigger rapid but not slow cell death. These results support the hypothesis that cell surface ART-2 uses NAD but not ADPR to attach ADP-ribosyl groups to the cell surface, and that these groups act as ligands for P2X7 receptors that then induce rapid cell death. Adding either NAD or ADPR also triggers a different set of mechanisms, not requiring ART-2 or P2X7 receptors that more slowly induce cell death.
Kawamura, H; Aswad, F; Minagawa, M; Malone, K; Kaslow, H; Koch, Nolte F.; Schott, W H.; Leiter, E H.; and Dennert, G, "P2X7 receptor-dependent and -independent T cell death is induced by nicotinamide adenine dinucleotide." (2005). Faculty Research 2000 - 2009. 1066.