sq-23377 and acetyl-aspartyl-glutamyl-valyl-aspartal

Fas-mediated apoptosis plays an important role in regulating the immune response in peripheral T cells. Restimulation of T cell blasts up-regulates Fas and Fas ligand expression, with subsequent interaction leading to cell death. Overexpression of Bcl-2 in tumor cells blocks apoptosis induced by many stimuli, but inhibition of Fas-mediated killing has not been consistently observed. To examine the behavior of Bcl-2 in normal cells, T cell blasts were transiently transfected with Bcl-2 and related gene products to determine the effect on apoptotic signaling. Transient overexpression of Bcl-2 in mouse and human T cell blasts did not block Fas-mediated apoptosis, whereas etoposide- and glucocorticoid-induced cytotoxicity was potently inhibited. Expression of Bcl-xL and adenovirus E1B 19K did not interfere with anti-Fas killing. In contrast, interleukin-1beta-converting enzyme family protease inhibitors Ac-DEVD-CHO and CrmA blocked Fas-mediated apoptosis. These results suggest that peripheral T cells use distinct apoptosis signaling pathways with differential sensitivity to Bcl-2 and interleukin-1beta-converting enzyme family protease inhibitors. Since T cells normally express Bcl-2 and Bcl-xL following activation, their inability to block Fas-mediated apoptosis may allow for the elimination of self-reactive cells and the appropriate regulation of immune responses.

Topics: Adenovirus E1B Proteins; Animals; Apoptosis; bcl-X Protein; Caspase 1; Cysteine Endopeptidases; Cytotoxicity, Immunologic; Dexamethasone; Etoposide; Fas Ligand Protein; fas Receptor; Gene Expression Regulation; Humans; Hybridomas; Ionomycin; Ionophores; Lymphocyte Activation; Membrane Glycoproteins; Mice; Mice, Inbred BALB C; Oligopeptides; Protease Inhibitors; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Recombinant Fusion Proteins; Signal Transduction; T-Lymphocytes, Cytotoxic; Tetradecanoylphorbol Acetate; Transfection