Characterization of LIGHT-induced apoptosis
| Autor: | Mei-Chieh Chen, 陳玫潔 |
|---|---|
| Rok vydání: | 2002 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 90 LIGHT is a member of TNF superfamily and is the ligand for LT-bR, HVEM and decoy receptor 3 (DcR3). LIGHT is a co-stimulatory factor to enhance the secretion of IFN-g by pre-activated T cells, and the cytotoxic effect of LIGHT is enhanced by the presence of IFN-g. However, the underlying mechanism for LIGHT/IFN-g is unclear. We found that caspases are activated by LIGHT/IFN-g on Hep3BT2 and HT-29 cells. However, neither general caspase inhibitor z-VAD-FMK nor BCL-2 is able to inhibit the cytotoxicity of LIGHT/IFN-g on Hep3BT2 and HT-29 cells. By contrast, the overexpession of BCL-2 further enhance the cytotoxicity of LIGHT/IFN-g due to the cleavage of BCL -2 at loop region to convert BCL-2 from anti-apoptotic to pro-apoptotic. However, the potent free radicals scavenger carboxyfullerenes (C60) effectively inhibit the activation of caspase as well as the inhibition of cell death, suggesting the importance of free radicals on LIGHT/IFN-g apoptosis. Interesting, we found that the apoptosis signal-regulating kinase 1 (ASK1) as well as the c-Jun NH2-terminal protein kinase (JNK) are also activated by the cross-linking of LT-bR induced by agonistic mAb, or by the overexpession of LT-bR on HeLa cells. The activation of ASK1 is via the recruitment of TRAF3 and TRAF5, but not TRAF2 or TRAF6, and is inhibited by free radical scavenger carboxyfullerenes (C60), indicating the presence of caspase-independent pathway triggered by LT-bR. Thus LIGHT might have the potential to become effective molecules to kill tumor cells which overexpress BCL-2 or have defect in the activation of caspase cascade in the future. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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