过表达BNIP3抑制PINK1缺失导致的果蝇异常

发布时间：2018-04-06 05:21

本文选题：BNIP3　切入点：PINK1　出处：《中南大学》2014年硕士论文

【摘要】：帕金森病(Parkinson's disease, PD)是一种常见的中枢神经系统退行性疾病,主要症状为运动障碍以及多巴胺能神经元丢失,其发病率在神经退行性疾病中居第二,仅次于阿尔茨海默病(Alzheimer's disease, AD)。近年来许多研究证明帕金森病的发病与细胞凋亡,线粒体自噬等因素紧密相关。有研究表明分属于Bcl-2蛋白家族BH3-only亚家族的BNIP3不仅与细胞凋亡有关,而且能与自噬相关蛋白LC3直接相互作用,参与诱导线粒体自噬,这些研究结果提示BNIP3可能也与PD的发病有关。目的：检测BNIP3是否与帕金森病发病相关。方法：通过显微注射获得BNIP3转基因果蝇UAS-BNIP3WT,利用GAL4-UAS系统特异性的在帕金森病果蝇模型(PINK1缺失的果蝇)的不同组织中过表达BNIP3,观察统计不同基因型果蝇的表型及某些功能指标。结果：1)在间接飞行肌中(IFMs)特异性过表达BNIP3能改善PINK1缺失果蝇的主要症状——翅膀异常和胸背部凹陷；2)特异性的在间接飞行肌过表达BNIP3能从线粒体水平(包括线粒体功能指标ATP含量及线粒体形态)改善PINK1缺失引起的果蝇异常；3)特异性的在多巴胺神经元中过表达BNIP3能抑制PINK1缺失导致的果蝇病理表型——多巴胺释放减少。结论：过表达BNIP3抑制PINK1缺失导致的果蝇异常,证实了BNIP3与帕金森病的发病相关。
[Abstract]:Parkinson's disease (Parkinson's disease PD) is a common neurodegenerative disease of the central nervous system, the main symptoms of dyskinesia and loss of dopaminergic neurons, the incidence of neurodegenerative diseases in second after Alzheimer's disease (Alzheimer's, disease, AD). In recent years, many studies have shown that the incidence of Parkinson's disease and cancer cell apoptosis, mitochondrial autophagy and other factors are closely related. Studies have shown that belong to BH3-only protein family Bcl-2 subfamily of BNIP3 is not only related to cell apoptosis, but also with the autophagy related protein LC3 interactions involved in the induction of mitochondrial autophagy, these results suggest that BNIP3 may be involved in the pathogenesis of PD.
Objective: to determine whether BNIP3 is associated with the onset of Parkinson's disease.
Methods: BNIP3 transgenic fruit fly UAS-BNIP3WT was obtained by microinjection. GAL4-UAS was used to overexpress BNIP3 in different tissues of Parkinson's disease Drosophila melanogaster model (PINK1 Drosophila melanogaster). The phenotypes and functional indexes of different genotype Drosophila melanogaster were observed.
Results: 1) in the indirect flight muscle (IFMs) specific overexpression of BNIP3 can improve the main symptoms of PINK1 deficient Drosophila wings and abnormal chest depression; 2) specificity in the indirect flight muscle expression of BNIP3 from mitochondria level (including mitochondrial function indexes of ATP content and mitochondrial morphology) caused by the lack of improvement in PINK1 the abnormal; 3) specificity in dopamine neurons in the overexpression of BNIP3 can inhibit the PINK1 due to the lack of pathological phenotype, Drosophila dopamine release decreased.
Conclusion: overexpression of BNIP3 inhibits the abnormalities of Drosophila caused by PINK1 deletion, and confirms that BNIP3 is associated with the incidence of Parkinson's disease.

【学位授予单位】：中南大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R742.5

【共引文献】