线粒体未折叠蛋白反应在Sir2抑制帕金森转基因果蝇中的作用

Role of mitochondrial unfolded protein response in Sir2 suppresses the neurodegeneration of PD transgenic Drosophila

目的探讨Sir2对帕金森病(PD)转基因果蝇是否有神经保护作用及与线粒体未折叠蛋白反应(UPRmt)的相关性。方法选用Mhc-GAL4启动子,利用经典的GAL4-UAS系统构建Mhc-GAL4/UAS系统Pink1B9PD转基因果蝇模型,通过遗传干预使Sir2在Mhc-GAL4/UAS系统PD转基因果蝇运动神经元内过表达,观察Sir2过表达对果蝇运动神经元变性是否具有神经保护作用,然后通过RNAi技术抑制UPRmt相关基因热休克蛋白60(Hsp60)、GCN-2的表达,观察Sir2过表达对抑制果蝇运动神经元变性的作用,以及验证这种作用是否与UPRmt相关。结果 Sir2过表达明显抑制了PD转基因果蝇运动神经元变性,显著改善了果蝇运动能力,而在UPRmt被抑制后,Sir2的保护作用明显减弱。结论Sir2对PD转基因果蝇具有神经保护作用,而这种神经保护作用与UPRmt相关。

Objective To investigate whether Sir2 has a neuroprotective effect on PD transgenic Drosophila and the relevance of UPR^mt. Methods The Mhc-GAL4 promoter and the classical GAL4-UAS system were used to construct PD transgenic Drosophila models-Pink1^B9 which could be expressed in Drosophila muscles. To investigate whether Sir2 overexpression in PD transgenic Drosophila of the Mhc-GAL4/UAS system by genetic intervention had neuroprotective effects on neurodegeneration. The chaperone Hsp60 and GCN-2 expression associated with UPR^mt by RNA interference were inhibited to observe the role of Sir2 overexpression in suppressing neurodegeneration in PD transgenic Drosophila and verify the correlation with UPR^mt. Results Sir2 overexpression significantly inhibited neurodegeneration in PD transgenic Drosophila and improved the athletic ability. The effect of Sir2 was weakened by inhibiting UPR^mt. Conclusion Sir2 overexpression has neuroprotective effects on PD transgenic Drosophila which is associated with UPR^mt.