Publication: N<sup>α</sup>-tosyl-L-phenylalanine chloromethyl ketone induces caspase-dependent apoptosis in transformed human B cell lines with transcriptional down-regulation of anti-apoptotic HS1-associated protein X-1
Issued Date
2009-10-09
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ISSN
1083351X
00219258
00219258
Other identifier(s)
2-s2.0-70350435090
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of Biological Chemistry. Vol.284, No.41 (2009), 27827-27837
Suggested Citation
Siriporn Jitkaew, Alicja Trebinska, Ewa Grzybowska, Göran Carlsson, Anders Nordström, Janne Lehtiö, Anne Sophie Fröjmark, Niklas Dahl, Bengt Fadeel N<sup>α</sup>-tosyl-L-phenylalanine chloromethyl ketone induces caspase-dependent apoptosis in transformed human B cell lines with transcriptional down-regulation of anti-apoptotic HS1-associated protein X-1. Journal of Biological Chemistry. Vol.284, No.41 (2009), 27827-27837. doi:10.1074/jbc.M109.027912 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/27133
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Title
N<sup>α</sup>-tosyl-L-phenylalanine chloromethyl ketone induces caspase-dependent apoptosis in transformed human B cell lines with transcriptional down-regulation of anti-apoptotic HS1-associated protein X-1
Abstract
Nα-Tosyl-L-phenylalanine chloromethylketone (TPCK) has been widely used to investigate signal transduction pathways that are involved in gene expression and cell survival/cell death. However, contradictory effects of TPCK on apoptosis have been reported, and the underlying signaling events leading to TPCK-induced promotion or prevention of apoptosis are not fully understood. Here, we show that TPCK induces caspase-dependent apoptosis in Epstein-Barr virus (EBV)-transformed human B cell lines with release of pro-apoptotic proteins from mitochondria. TPCK treatment also results in down-regulation of the anti-apoptotic proteins, cIAP1, cIAP2, and HAX-1, and caspase-dependent cleavage of the anti-apoptotic proteins, Bcl-2 and XIAP. Quantitative PCR analysis confirmed that the TPCK-induced down-regulation of HAX-1 occurred at the transcriptional level, and experiments using the specific pharmacological inhibitor, Bay 11-7082, suggested that HAX-1 expression is subject to regulation by the transcription factor, NF-αB. B cell lines derived from patients with homozygous HAX1 mutations were more sensitive to TPCK-induced apoptosis when compared with normal donor cell lines. Furthermore, N-acetylcysteine effectively blocked TPCK-induced apoptosis in EBVtransformed B cell lines and prevented the down-regulation or cleavage of anti-apoptotic proteins. Taken together, our studies demonstrate that TPCK induces apoptosis in human B cell lines and exerts multiple effects on pro- and anti-apoptotic factors. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.