Role of Telomerase in Amyloid beta-Induced Apoptosis
| Autor: | Chin-Yen Wu, 吳金燕 |
|---|---|
| Rok vydání: | 2008 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 96 Amyloid beta peptide (Abeta) has been shown to induce cell death, however the apoptotic mechanism is still undefined. In the present study, Abeta25-35 and Abeta1-40, but not Abeta1-16 and Abeta35-25, dose-dependently reduce the telomerase activity in U87-MG, C6 glioma, Neuro-2a, primary murine cerebral endothelial cells(CECs) by TRAP assay in according with apoptosis induction. A decrease in Bcl-2 protein and an increase in Bax protein with an activation of caspase 3, PARP, and D4-GDI protein via cleavage induction were detected in Abeta25-35-treated CECs. Additionally, Abeta25-35 stimulation reduced the expression of endogenous HSP90 and its client proteins including Akt, TERT, Cdk4, and p53. Adding HSP90 inhibitors geldanamycin (GA) and radicicol (RD) enhanced the telomerase inhibition and apoptosis induction elicited by Abeta25-35. Furthermore, a decrease in the phosphorylated Akt protein by Abeta25-35 was detected in CECs, and application of PI3k/Akt inhibitor LY294002 reduced telomerase activity. Induction of protein ubiquitination in CECs by Abeta25-35 were identified, and decreases in HSP90 and TERT protein, and telomerase activity by Abeta25-35 were blocked by an addition of a proteasome inhibitor MG132. These results suggest that inhibition of telomerase activity via a HSP90-dependent manner plays an important role in Abeta25-35-induced apoptosis. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
| Externí odkaz: |
|