Studies on reduction of avian reovirus replication and apoptosis in culture cells by proteasome inhibitor MG132
| Autor: | Yu-Tsen Chen, 陳俞岑 |
|---|---|
| Rok vydání: | 2008 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 96 Avian reovirus (ARV) belongs to Orthoreovirus genus of Reoviridae family, and replicates in the cytoplasm of infected cells. ARVs are icosahedral shaped non-enveloped viruses. Infection with ARV causes severe cytopathic effects (CPE) and apoptosis in both avian and mammalian cells. For the past several years, our laboratory has been demonstrated that the σC protein of ARV could induce apoptosis in culture cells and discovered that it is an apoptotin. In 2007, our team also demonstrated that ARV-induced apoptosis through src protein kinase to activate p53. It was also discovered that p53 regulates Bax expression, and translocation to the mitochondria leading to cytochrome c release into the cytoplasm, activating the caspase pathway that finally leads to cell apoptosis. This study was therefore aimed at elucidating whether ARV also utilizes the ubiquitin-proteasome pathway for it’s own benefit and other mechanisms regulation for cells. Using the proteasome inhibitor MG132 to inhibit the cellular proteasome system, we found that MG132 could reduce ARV-induced cytopathic effect, virus titer, viral RNA transcription, viral protein expression and apoptosis. When we tested cellular translation and virus internalization, we observed that cellular translation was normal and virus internalization was also not blocked, suggesting that MG132 could affect viral replication. Finally we discovered MG132 could block ARV-induced phosphorylation of p53 on ser-46, caspase3 activity and DNA ladder leading to complete inhibition of ARV-induced apoptosis. This study for the first time demonstrates that MG132 could block ARV replication and apoptosis induction. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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