Taurine Monochloramine Activates a Cell Death Pathway Involving Bax and Caspase-9

Abstract

Taurine is an abundant free amino acid that interacts with the potent oxidant hypochlorous acid to form the less toxic and more stable oxidant taurine monochloramine (TauNHCl). TauNHCl has diverse cellular effects ranging from inhibiting the production of proinflammatory mediators to inhibiting cell proliferation and inducing cell death. We hypothesized that TauNHCl could activate a cell death pathway involving Bcl-2 members and the activation of caspase proteases. FL5.12 cells are lymphocytic cells that undergo apoptosis following interleukin-3 (IL-3) withdrawal. Therefore, cell death following TauNHCl treatment of FL5.12 cells was compared and contrasted with IL-3 withdrawal. We found that TauNHCl treatment activates a cell death pathway with kinetics very similar to IL-3 withdrawal. TauNHCltreated cells undergo an annexin V-positive/propidium iodide-negative phase of death consistent with apoptosis. TauNHCl treatment results in a conformational change in BAX that is associated with its activation. Both Bcl-2 and, to a lesser degree, the dominant negative form of caspase-9 inhibit cell death following TauNHCl treatment. In contrast with IL-3 withdrawal, TauNHCl treatment of FL5.12 cells results in a rapid cell cycle arrest that is cell cycle phase-independent. These results demonstrate that TauNHCl treatment induces a rapid, cell cycle-independent proliferative arrest followed by the activation of a cell death pathway involving Bcl-2 family members and caspase activation.

Taurine chloramine induces apoptosis in human osteosarcoma cell lines

“…A recent study by Emerson et al has shown that NCT dosedependently inhibits inflammatory cytokine release and can induce cell death in the murine hematopoietic prolymphocytic B cell line FL5.12 via mitochondrial damage inducing the classic mitochondrial apoptosis pathway. 11 Previously NCT has been shown to mediate apoptosis in the Burkitt's lymphoma cell lines JLP-119 10 and BL-41. 17 The remarkable tolerability of NCT has been shown in various in vitro and in vivo studies, including animal models and clinical studies.…”

“…[10][11][12][13] Omnivores ingest a mean daily amount of 58 mg taurine, which occurs naturally in food, especially meat and seafood. 12 It plays an important role in several essential biological processes, such as development of the central nervous system and retina, calcium modulation, membrane stabilization, reproduction, and immunity.…”

“…13,14 This substance inhibits the intracellular transcription of nitric oxide synthase and the production of nitric oxide and switches the less advantageous necrosis to the more physiologically beneficial apoptosis in a variety of cells. 11 The production of NCT, a more stable and less toxic oxidant, in the cytosol is regarded to be a detoxification reaction. 15 Previously, NCT has been shown to induce apoptosis in human B lymphoma cells 10 and murine hematopoietic prolymphocytic B cells through mitochondrial damage.…”

“…15 Previously, NCT has been shown to induce apoptosis in human B lymphoma cells 10 and murine hematopoietic prolymphocytic B cells through mitochondrial damage. 11 The objective of this study was to assess the effect of NCT on proliferation and viability of three different osteosarcoma cell lines. We hypothesized that NCT would induce apoptotic cell death via the mitochondrial pathway in these tumor cells and thereby decrease cell viability in a dose-and time-dependent manner.…”

Early Events in Apoptosis Induction in Polymorphonuclear Leukocytes

“…Myeloperoxidase deficiency suppresses also PMN apoptosis (Tsurubuchi et al, 2001;Milla et al, 2004). Several myeloperoxidase products such as hypothiocyanite, monochloramine and taurine chloramine are potent inducers of apoptosis (Emerson et al, 2005;Lloyd et al, 2008;Ogino et al, 2009). …”