Taurine monochloramine activates a cell death pathway involving Bax and Caspase-9.
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. TauNHCl-treated 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.
Emerson
Derek K
DK
Department of Pathology, The University of Iowa Roy J. and Lucille P. Carver College of Medicine, Iowa City, Iowa 52242, USA.
McCormick
Michael L
ML
Schmidt
Jennifer A
JA
Knudson
C Michael
CM
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002999:Clone Cells; D018836:Inflammation Mediators / Q000494:pharmacology*; D051379:Mice; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein
C494827:Bax protein, mouse; D018836:Inflammation Mediators; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D013654:Taurine; C043410:N-chlorotaurine; C506434:Casp9 protein, mouse; D053453:Caspase 9; D020169:Caspases