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Can application of serine protease inhibitors TPCK and TLCK provide evidence for possible involvement of serine protease Omi/HtrA2 in imatinib mesylate-induced cell death of BCR-ABL-positive human leukemia cells?

Leukemia volume 19, pages 1085–1087 (2005)Cite this article

TO THE EDITOR

Apoptosis was originally defined as a mode of cell death with specific morphology.1 Since the discovery of caspase proteases, it has been evident that caspase activation was indispensable for apotosis to occur in various mammalian cell types. First reports in the early 1990s demonstrated that the broad-spectrum caspase inhibitors such as z-VAD-fmk could effectively block apoptosis in several animal cell death models.2 Later on, it was rather surprisingly demonstrated that caspase inhibitors were unable to prevent cells from death; cells still died, although more slowly while exhibiting necrosis-like morphology.3 Further research revealed that mitochondria play crucial role in both caspase-dependent and -independent commitment to cell death. Various extracellular and intracellular insults may eventually lead to the release of proteins that reside in intermembrane space of mitochondria resulting in cell death. Some of these proteins including cytochrome c and Smac/DIABLO act as caspase activators. The others, including AIF (apoptosis-inducing factor) and endonuclease G, contribute to caspase-independent cell death. Omi/HtrA2, a serine protease that also reside in intermembrane mitochondrial space, can act in both ways.4

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Acknowledgements

This work was supported by the Czech Grant Agency, Grant GA301/04/1239.

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  1. Department of Biology, Faculty of Medicine, Palacky University, Olomouc, Czech Republic

    P Mlejnek

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Mlejnek, P. Can application of serine protease inhibitors TPCK and TLCK provide evidence for possible involvement of serine protease Omi/HtrA2 in imatinib mesylate-induced cell death of BCR-ABL-positive human leukemia cells?. Leukemia 19, 1085–1087 (2005). https://doi.org/10.1038/sj.leu.2403701

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