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| Item Type: | Article |
|---|---|
| Title: | Type I and type II reactions in TRAIL-induced apoptosis - results from dose-response studies |
| Creators Name: | Rudner, J., Jendrossek, V., Lauber, K., Daniel, P.T., Wesselborg, S. and Belka, C. |
| Abstract: | Death receptor-induced apoptosis is paradigmatically mediated via the recruitment of FADD adapter molecule to the ligand/receptor complex and subsequent activation of caspase-8. However, several observations provided evidence that components of the mitochondrial apoptosis pathway are involved in death receptor-mediated apoptosis. In this regard, caspase-8-mediated activation of Bid induces the release of cytochrome c from the mitochondria, which, in turn, triggers the formation of the apoptosome protein complex, resulting in the activation of caspase-9. Whereas Bax or Bak were shown to be required for the proapoptotic effect of Bid, Bcl-2 was described to interfere with its action. Up to now, contradictory results regarding the role of Bcl-2 in TRAIL-induced apoptosis have been published. In order to study the influence of Bcl-2 on TRAIL-induced cell death more detailed, we utilized a tetracycline-regulated Bcl-2 expression system in Jurkat T cells. After having analysed the dose response for TRAIL-induced activation of caspase-8, -9, -3, breakdown of the mitochondrial membrane potential, and changes in the apoptotic morphology in cells expressing different Bcl-2 levels, we conclude that overexpression of Bcl-2 mediates a partial resistance towards lower doses of TRAIL that can be overcome when higher doses of TRAIL are applied. Thus, the requirement of the mitochondrial pathway for death receptor-induced apoptosis in type II cells should be reconsidered, since the protective effect of Bcl-2 is limited to lower TRAIL doses or early observation time points. |
| Keywords: | TRAIL, BCL-2, Apoptosis |
| Source: | Oncogene |
| ISSN: | 0950-9232 |
| Publisher: | Nature Publishing Group |
| Volume: | 24 |
| Page Range: | 130-140 |
| Date: | 6 January 2005 |
| Official Publication: | https://doi.org/10.1038/sj.onc.1208191 |
| PubMed: | View item in PubMed |
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