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Tributyltin (TBT) induces ultra-rapid caspase activation independent of apoptosome formation in human platelets

Oncogene volume 22, pages 775–780 (2003)Cite this article

Abstract

Activation of caspases has been demonstrated to be involved in thrombocytopenia and prolonged storage of platelet concentrates. Platelets represent enucleate cells that comprise all elements of the mitochondrial apoptosis pathway. However, no apoptotic stimuli capable of activating the endogenous caspase cascade have been identified so far. Using tributyltin (TBT) we could identify a compound that is capable of activating caspase-9 and -3 in platelets. Recent studies implicate that TBT induces apoptosis via the mitochondrial signaling pathway that is characterized by the formation of a high-molecular-weight complex (apoptosome) containing the adapter protein Apaf-1 and active caspase-9. Interestingly, addition of TBT induced the activation of caspase-9 in an ultra-rapid kinetic within the first 2 min. In addition, size exclusion chromatography revealed that TBT-mediated processing of caspase-9 occurs in the absence of the apoptosome. Thus, these data implicate that TBT induces the activation of caspase-9 by a mechanism not involving the formation of the apoptosome.

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Acknowledgements

We thank Dr Y Lazebnik for providing mAb against caspase-9. This work was supported by grants from the Federal Ministry of Education, Science, Research and Technology (Fö. 01KS9602), and the Interdisciplinary Center of Clinical Research Tübingen (IZKF) and from the Deutsche Forschungsgemeinschaft (WE-1801/1). C Berg acknowledges a fellowship from the Fortune Program of the University of Tübingen.

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Author notes

  1. Christoph P Berg, Andreas Rothbart and Kirsten Lauber: These authors share equal first authorship

  2. Klaus Schulze-Osthoff and Sebastian Wesselborg: Both authors share equal senior authorship

Authors and Affiliations

  1. Department of Internal Medicine I, University of Tübingen, Germany

    Christoph P Berg, Andreas Rothbart, Kirsten Lauber, Gerburg M Stein & Sebastian Wesselborg

  2. Division of Immunology and Cell Biology, University of Münster, Germany

    Ingo H Engels, Reiner U Jänicke & Klaus Schulze-Osthoff

  3. Department of Radiation and Oncology, University of Tübingen, Germany

    Claus Belka

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  1. Christoph P Berg
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Correspondence to Sebastian Wesselborg.

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Berg, C., Rothbart, A., Lauber, K. et al. Tributyltin (TBT) induces ultra-rapid caspase activation independent of apoptosome formation in human platelets. Oncogene 22, 775–780 (2003). https://doi.org/10.1038/sj.onc.1206221

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