Abstract
The serine protease inhibitor N-α-tosyl-L-phenylalanine chloromethyl ketone (TPCK) can interfere with cell-cycle progression and has also been shown either to protect cells from apoptosis or to induce apoptosis. We tested the effect of TPCK on two transformed T-cell lines. Both Jurkat T-cells and Theileria parva-transformed T-cells were shown to be highly sensitive to TPCK-induced growth arrest and apoptosis. Surprisingly, we found that the thiol antioxidant, N-acetylcysteine (NAC), as well as L- or D-cysteine blocked TPCK-induced growth arrest and apoptosis. TPCK inhibited constitutive NF-κB activation in T. parva-transformed T-cells, with phosphorylation of IκBα and IκBβ being inhibited with different kinetics. TPCK-mediated inhibition of IκB phosphorylation, NF-κB DNA binding and transcriptional activity were also prevented by NAC or cysteine. Our observations indicate that apoptosis and NF-κB inhibition induced by TPCK result from modifications of sulphydryl groups on proteins involved in regulating cell survival and the NF-κB activation pathway(s).
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Heussler, V., Fernandez, P., Machado, J. et al. N-acetylcysteine blocks apoptosis induced by N-α-tosyl-L-phenylalanine chloromethyl ketone in transformed T-cells. Cell Death Differ 6, 342–350 (1999). https://doi.org/10.1038/sj.cdd.4400501
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DOI: https://doi.org/10.1038/sj.cdd.4400501
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