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).
Kontny
Ewa
E
Department of Pathophysiology and Immunology, Institute of Rheumatology, Warsaw, Poland. zpatiir@warman.com.pl
Chorazy-Massalska
Magdalena
M
Rudnicka
Weronika
W
Marcinkiewicz
Janusz
J
Maśliński
Włodzimierz
W
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D002402:Cathepsin D / Q000378:metabolism; D016923:Cell Death / Q000502:physiology*; D002478:Cells, Cultured; D024161:Collagen Type XI / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013583:Synovial Membrane / Q000166:cytology; D013654:Taurine / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D019014:fas Receptor / Q000276:immunology
C499319:COL11A2 protein, human; D024161:Collagen Type XI; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; D013654:Taurine; D020169:Caspases; D002402:Cathepsin D