Taurine chloramine, an oxidant derived from neutrophils, induces apoptosis in human B lymphoma cells through mitochondrial damage.
Taurine chloramine (TN-Cl) is one of the most abundant compounds generated by activated neutrophils. In contrast to HOCl, which causes necrosis, TN-Cl is a potent inducer of apoptosis in tumor cells. Here we show that the apoptosis induced by TN-Cl in human B lymphoma cells is dependent upon oxidant-mediated mitochondrial damage, a decrease in mitochondrial membrane potential, and caspase-9 activation. Further, we show that TN-Cl is taken up into the cells and is concentrated in the mitochondria, where it induces opening of the permeability transition pore and mitochondrial swelling. Identical activity is seen upon treatment of isolated mitochondria with TN-Cl and is blocked by the permeability transition pore inhibitors bongkrekic acid and cyclosporin A, as well as by the sulfhydryl-reducing agent tris(2-carboxyethyl)-phosphine. The data suggest that TN-Cl causes apoptosis through direct damage to the mitochondria.
Klamt
Fabio
F
Laboratory of Biochemistry, Division of Therapeutic Proteins, Center of Drug Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA.
Shacter
Emily
E
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D017209:Apoptosis; D001865:Bongkrekic Acid / Q000494:pharmacology; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D016923:Cell Death; D045744:Cell Line, Tumor; D016572:Cyclosporine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007202:Indicators and Reagents / Q000494:pharmacology; D018836:Inflammation Mediators / Q000494:pharmacology; D007425:Intracellular Membranes / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000378:metabolism / Q000473:pathology*; D008564:Membrane Potentials; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology*; D009504:Neutrophils / Q000378:metabolism*; D016877:Oxidants / Q000737:chemistry / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism; D010539:Permeability; D011419:Propidium / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013997:Time Factors; D014634:Valinomycin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D018836:Inflammation Mediators; D016877:Oxidants; D013438:Sulfhydryl Compounds; D001865:Bongkrekic Acid; D013654:Taurine; D014634:Valinomycin; D011419:Propidium; C043410:N-chlorotaurine; D016572:Cyclosporine; C506433:CASP9 protein, human; D053453:Caspase 9; D020169:Caspases; D010100:Oxygen