Tributyltin (TBT) induces ultra-rapid caspase activation independent of apoptosome formation in human platelets
| Autor: | Reiner U. Jänicke, Sebastian Wesselborg, Gerburg M. Stein, Kirsten Lauber, Andreas Rothbart, Christoph P. Berg, Claus Belka, Ingo H. Engels, Klaus Schulze-Osthoff |
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| Rok vydání: | 2003 |
| Předmět: |
Blood Platelets
Caspase-9 Cancer Research Time Factors biology Signal transducing adaptor protein Apoptosis Mitochondrion Caspase 9 Cell biology Enzyme Activation chemistry.chemical_compound chemistry Biochemistry Caspases Genetics biology.protein Tributyltin Humans Apoptosome Trialkyltin Compounds Signal transduction Molecular Biology Caspase |
| Zdroj: | Oncogene. 22:775-780 |
| ISSN: | 1476-5594 0950-9232 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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