The cathepsin B inhibitor z-FA-CMK induces cell death in leukemic T cells via oxidative stress
In: Naunyn-Schmiedeberg's Archives of Pharmacology, Jg. 391 (2017-10-31), S. 71-82
Online
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Zugriff:
The cathepsin B inhibitor benzyloxycarbonyl-phenylalanine-alanine-chloromethyl ketone (z-FA-CMK) was recently found to induce apoptosis at low concentrations in Jurkat T cells, while at higher concentrations, the cells die of necrosis. In the present study, we showed that z-FA-CMK readily depletes intracellular glutathione (GSH) with a concomitant increase in reactive oxygen species (ROS) generation. The toxicity of z-FA-CMK in Jurkat T cells was completely abrogated by N-acetylcysteine (NAC), suggesting that the toxicity mediated by z-FA-CMK is due to oxidative stress. We found that L-buthionine sulfoximine (BSO) which depletes intracellular GSH through the inhibition of GSH biosynthesis in Jurkat T cells did not promote ROS increase or induce cell death. However, NAC was still able to block z-FA-CMK toxicity in Jurkat T cells in the presence of BSO, indicating that the protective effect of NAC does not involve GSH biosynthesis. This is further corroborated by the protective effect of the non-metabolically active D-cysteine on z-FA-CMK toxicity. Furthermore, in BSO-treated cells, z-FA-CMK-induced ROS increased which remains unchanged, suggesting that the depletion of GSH and increase in ROS generation mediated by z-FA-CMK may be two separate events. Collectively, our results demonstrated that z-FA-CMK toxicity is mediated by oxidative stress through the increase in ROS generation.
Titel: |
The cathepsin B inhibitor z-FA-CMK induces cell death in leukemic T cells via oxidative stress
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Autor/in / Beteiligte Person: | Liow, K. Y. ; Chow, Sek C. |
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Zeitschrift: | Naunyn-Schmiedeberg's Archives of Pharmacology, Jg. 391 (2017-10-31), S. 71-82 |
Veröffentlichung: | Springer Science and Business Media LLC, 2017 |
Medientyp: | unknown |
ISSN: | 1432-1912 (print) ; 0028-1298 (print) |
DOI: | 10.1007/s00210-017-1436-6 |
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