The cathepsin B inhibitor, z-FA-CMK is toxic and readily induced cell death in human T lymphocytes.
In: Toxicology & Applied Pharmacology, Jg. 272 (2013-11-01), Heft 3, S. 559-567
academicJournal
Zugriff:
Abstract: The cathepsin B inhibitor, benzyloxycarbonyl-phenylalanine-alanine-chloromethylketone (z-FA-CMK) was found to be toxic and readily induced cell death in the human T cell line, Jurkat, whereas two other analogs benzyloxycarbonyl-phenylalanine-alanine-fluoromethylketone (z-FA-FMK) and benzyloxycarbonyl-phenylalanine-alanine-diazomethylketone (z-FA-DMK) were not toxic. The toxicity of z-FA-CMK requires not only the CMK group, but also the presence of alanine in the P1 position and the benzyloxycarbonyl group at the N-terminal. Dose–response studies showed that lower concentrations of z-FA-CMK induced apoptosis in Jurkat T cells whereas higher concentrations induced necrosis. In z-FA-CMK-induced apoptosis, both initiator caspases (-8 and -9) and effector caspases (-3, -6 and -7) were processed to their respective subunits in Jurkat T cells. However, only the pro-form of the initiator caspases were reduced in z-FA-CMK-induced necrosis and no respective subunits were apparent. The caspase inihibitor benzyloxycarbonyl-valine-alanine-aspartic acid-(O-methyl)-fluoromehylketone (z-VAD-FMK) inhibits apoptosis and caspase processing in Jurkat T cells treated with low concentration of z-FA-CMK but has no effect on z-FA-CMK-induced necrosis and the loss of initiator caspases. This suggests that the loss of initiator caspases in Jurkat T cells during z-FA-CMK-induced necrosis is not a caspase-dependent process. Taken together, we have demonstrated that z-FA-CMK is toxic to Jurkat T cells and induces apoptosis at low concentrations, while at higher concentrations the cells die of necrosis. [Copyright &y& Elsevier]
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The cathepsin B inhibitor, z-FA-CMK is toxic and readily induced cell death in human T lymphocytes.
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Autor/in / Beteiligte Person: | Liow, K.Y. ; Chow, S.C. |
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Zeitschrift: | Toxicology & Applied Pharmacology, Jg. 272 (2013-11-01), Heft 3, S. 559-567 |
Veröffentlichung: | 2013 |
Medientyp: | academicJournal |
ISSN: | 0041-008X (print) |
DOI: | 10.1016/j.taap.2013.07.022 |
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