Induction of the pyridine nucleotide synthesis pathway in mitogen-stimulated human T-lymphocytes*1

Pre-B-cell colony-enhancing factor, whose expression is up-regulated in activated lymphocytes, is a nicotinamide phosphoribosyltransferase, a cytosolic enzyme involved in NAD biosynthesis

“…4). In conclusion, the present data are in keeping with previous observations indicating that mitogenic stimulation of human T cells leads to a 5-20-fold increase in cell-associated NAmPRTase activity [36], suggesting that induction of PBEF synthesis may represent a physiological response to meet the increased demand of NAD in proliferating cells. The identification of the gene and protein responsible for the NAmPRTase activity in mammals will allow a deeper understanding of the role of NAD biosynthesis in higher organisms and its potential role as a signaling molecule in the immune system.…”

Crystal Structure of Visfatin/Pre-B Cell Colony-enhancing Factor 1/Nicotinamide Phosphoribosyltransferase, Free and in Complex with the Anti-cancer Agent FK-866

“…In human T cells, for example, mitogenic stimulation leads to a 5-20-fold increase in cell-associated NAmPRTase activity. 16 In addition, NAD-dependent protein deacetylase activity is essential for vascular smooth muscle cell maturation and is increased by the NAmPRTase activity of visfatin. 6 Selective inhibition of NAmPRTase induces delayed apoptotic cell death in human hepatocarcinoma cells, 10 suggesting visfatin may be a useful target in the treatment of liver cancer.…”

NAD+ Levels Control Ca2+ Store Replenishment and Mitogen-induced Increase of Cytosolic Ca2+ by Cyclic ADP-ribose-dependent TRPM2 Channel Gating in Human T Lymphocytes

“…Indeed, the addition of either NAM or NA rescues the NAD ϩ depletion caused by FK866 in human PBLs (11). Altogether, the strong increase in Nampt and Naprt1 levels in activated T lymphocytes (5)(6)(7)(8)11) and the fact that Nampt inhibition by FK866 negatively affects T cell function and survival (11) indicate that NAD ϩ availability is critically important for the capacity of human T lymphocytes to respond to antigenic stimuli. Accordingly, strategies aimed at lowering NAD ϩ levels have been proposed to treat immune disorders (11,14).…”