Cytotoxicity of taurine metabolites depends on the cell type.

We report that the effect of Tau-Cl on the cell fate strongly depends on the cellular context. In leukemic Jurkat cells Tau-Cl (> 200 microM) triggers mitochondrial, p53-independent apoptosis and amplifies PCD induced by anti-Fas treatment. In contrast, Tau-Cl affects RA FLS in a dose-dependent manner. At the noncytotoxic (200-400 microM) concentrations it induces: (i) p53-dependent growth arrest (Kontny et al., 2005), and (ii) Bax translocation and caspase 9 activity. Although the last events are characteristic for apoptotic state, there is not execution of RA FLS apoptosis, probably due to simultaneous inhibition of caspase 3 activity and prevention of PARP degradation. The last two events suggest an excessive ATP deprivation in Tau-Cl-treated RA FLS. At sufficiently high concentrations (> or = 500 microM) Tau-Cl causes therefore necrosis of these cells. Altogether our results suggest that Tau-Cl is able to eliminate the cells with both functional (RA FLS) and mutated (Jurkat) p53 tumor suppressor. This observation is clinically relevant because Tau-Cl is used in many animal inflammatory models and its sodium salt (used in this study) has been introduced to human therapy (Gottardi and Nagl, 2002; Teuchner et al., 2005).

[1]  P. Krammer,et al.  CD95's deadly mission in the immune system , 2000, Nature.

[2]  J. Pullar,et al.  Hypochlorous acid causes caspase activation and apoptosis or growth arrest in human endothelial cells. , 1999, The Biochemical journal.

[3]  M. Haas,et al.  Frequent mutations in the p53 tumor suppressor gene in human leukemia T-cell lines , 1990, Molecular and cellular biology.

[4]  A. Kettle,et al.  Substrates and products of eosinophil peroxidase. , 2001, The Biochemical journal.

[5]  P. Vandenabeele,et al.  Toxic proteins released from mitochondria in cell death , 2004, Oncogene.

[6]  K. Itoh,et al.  Central role of mitochondria and p53 in Fas-mediated apoptosis of rheumatoid synovial fibroblasts. , 2004, Rheumatology.

[7]  W. Maśliński,et al.  The effect of taurine and its metabolites on the pathogenic functions of rheumatoid arthritis fibroblast-like synoviocytes , 2004 .

[8]  Ahmi Ben-Yehudah,et al.  Mechanism of action of interleukin-2 (IL-2)-Bax, an apoptosis-inducing chimaeric protein targeted against cells expressing the IL-2 receptor. , 2003, The Biochemical journal.

[9]  E. Shacter,et al.  Distinct Modes of Cell Death Induced by Different Reactive Oxygen Species , 2002, The Journal of Biological Chemistry.

[10]  W. Maśliński,et al.  Protein kinase c-dependent pathway is critical for the production of pro-inflammatory cytokines (TNF-alpha, IL-1beta, IL-6). , 1999, Cytokine.

[11]  G. Firestein.  Invasive fibroblast-like synoviocytes in rheumatoid arthritis. Passive responders or transformed aggressors? , 1996, Arthritis and rheumatism.

[12]  Yi-Te Hsu,et al.  Movement of Bax from the Cytosol to Mitochondria during Apoptosis , 1997, The Journal of cell biology.

[13]  Yubo Sun,et al.  p53, proto-oncogene and rheumatoid arthritis. , 2002, Seminars in arthritis and rheumatism.

[14]  V. Dawson,et al.  Role of AIF in caspase-dependent and caspase-independent cell death , 2004, Oncogene.

[15]  Y. Hsu,et al.  Cytosol-to-membrane redistribution of Bax and Bcl-X(L) during apoptosis. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[16]  K. Tipton,et al.  Conversion of taurine into N-chlorotaurine (taurine chloramine) and sulphoacetaldehyde in response to oxidative stress. , 1998, The Biochemical journal.

[17]  P. Bozeman,et al.  Oxidation of Bromide by the Human Leukocyte Enzymes Myeloperoxidase and Eosinophil Peroxidase , 1995, The Journal of Biological Chemistry.

[18]  P. Robbins,et al.  Gene transfer of p53 to arthritic joints stimulates synovial apoptosis and inhibits inflammation. , 2001, Molecular therapy : the journal of the American Society of Gene Therapy.

[19]  B. Chain,et al.  Regulation of murine dendritic cell functions in vitro by taurine chloramine, a major product of the neutrophil myeloperoxidase–halide system , 1999, Immunology.

[20]  G. Firestein,et al.  Invasiveness of synovial fibroblasts is regulated by p53 in the SCID mouse in vivo model of cartilage invasion. , 2001, Arthritis and rheumatism.

[21]  M. Koprowski,et al.  Is there a role of taurine bromamine in inflammation? Interactive effects with nitrite and hydrogen peroxide , 2004, Inflammation Research.

[22]  H. Ulmer,et al.  Tolerability and efficacy of N-chlorotaurine in epidemic keratoconjunctivitis--a double-blind, randomized, phase-2 clinical trial. , 2005, Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics.

[23]  S. Chiou,et al.  Survivin - an anti-apoptosis protein: its biological roles and implications for cancer and beyond. , 2003, Medical science monitor : international medical journal of experimental and clinical research.

[24]  D. Green,et al.  Regulation of joint destruction and inflammation by p53 in collagen-induced arthritis. , 2002, The American journal of pathology.

[25]  W. Maśliński,et al.  Anti-inflammatory Activities of Taurine Chloramine , 2003 .

[26]  W. Maśliński,et al.  Taurine chloramine modulates cytokine production by human peripheral blood mononuclear cells , 2002, Amino Acids.

[27]  T. Ogino,et al.  Monochloramine enhances Fas (APO‐1/CD95)‐induced apoptosis in Jurkat T cells , 2000, Journal of leukocyte biology.

[28]  E. Kontny,et al.  Effect of taurine chloramine, the product of activated neutrophils, on the development of collagen-induced arthritis in DBA 1/J mice , 2002, Amino Acids.

[29]  W. Maśliński,et al.  Taurine chloramine inhibition of cell proliferation and cytokine production by rheumatoid arthritis fibroblast-like synoviocytes. , 1999, Arthritis and rheumatism.

[30]  M. Jäättelä,et al.  Multiple cell death pathways as regulators of tumour initiation and progression , 2004, Oncogene.

[31]  C. Harris,et al.  p53: 25 years after its discovery. , 2004, Trends in pharmacological sciences.

[32]  E. Slee,et al.  To die or not to die: how does p53 decide? , 2004, Oncogene.

[33]  A. Kettle,et al.  Initiation of rapid, P53-dependent growth arrest in cultured human skin fibroblasts by reactive chlorine species. , 2000, Archives of biochemistry and biophysics.

[34]  W. Maśliński,et al.  Taurine chloramine inhibits proliferation of rheumatoid arthritis synoviocytes by triggering a p53-dependent pathway , 2006, Inflammation Research.

[35]  John M Abrams,et al.  Caspase activation – stepping on the gas or releasing the brakes? Lessons from humans and flies , 2004, Oncogene.

[36]  G. Melino,et al.  Regulation of the apoptosis–necrosis switch , 2004, Oncogene.

[37]  R. Olszanecki,et al.  Taurine chloramine and taurine bromamine induce heme oxygenase-1 in resting and LPS-stimulated J774.2 macrophages , 2004, Amino Acids.

[38]  G. Firestein.  Evolving concepts of rheumatoid arthritis , 2003, Nature.

[39]  M. Nagl,et al.  Chemical Properties of N‐Chlorotaurine Sodium, a Key Compound in the Human Defence System , 2002, Archiv der Pharmazie.

[40]  W. Maśliński,et al.  Selective inhibition of cyclooxygenase 2-generated prostaglandin E2 synthesis in rheumatoid arthritis synoviocytes by taurine chloramine. , 2003, Arthritis and rheumatism.

[41]  C. Knudson,et al.  Taurine Monochloramine Activates a Cell Death Pathway Involving Bax and Caspase-9* , 2005, Journal of Biological Chemistry.

[42]  E. Park,et al.  Taurine: new implications for an old amino acid. , 2003, FEMS microbiology letters.

[43]  P. Hammerman,et al.  Akt-Directed Glucose Metabolism Can Prevent Bax Conformation Change and Promote Growth Factor-Independent Survival , 2003, Molecular and Cellular Biology.