过表达PINK1改善SCA3/MJD转基因果蝇模型的线粒体功能  

Overexpression of PINK1 Improve Mitochondrial Function in SCA3/MJD Transgenic Drosophila Model

作　　者：曾爱源[1] 李琼[1] 黄强[1] 陈梅玲[1] 林小慧[1] 李清华[1,2] 

机构地区：[1]桂林医学院附属医院神经内科,桂林541001 [2]桂林医学院,桂林541004

出　　处：《中国生物化学与分子生物学报》2015年第1期88-95,共8页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金项目(No.81241128;No.81160163;No.81360488);广西自然科学基金项目(No.2011GXNSFA018232;No.2012jjA A40155)~~

摘　　要：脊髓小脑性共济失调3型(SCA3/MJD),是一种因致病基因MJD1编码区内CAG异常重复扩增所致的常染色体显性遗传迟发性神经退行性疾病.已知PINK1蛋白可通过抗氧化稳定线粒体,阻止帕金森疾病的发生,但其在SCA3/MJD中的作用尚不清楚.本文旨在探索过表达PINK1对SCA3/MJD转基因果蝇模型的保护作用.本研究利用Mhc-Gal4启动子表达致病蛋白质片段(MJDtr-Q78)获得SCA3/MJD果蝇模型,分别运用过表达PINK1和RNA干扰PINK1研究其在SCA3/MJD果蝇模型中的功能.结果显示,疾病模型组翅膀异常率增高,线粒体呈过度融合状态,ATP值降低;PINK1 RNA干扰组翅膀异常率明显增高,线粒体呈显著过度融合状态,ATP值明显降低;PINK1过表达组翅膀异常率明显降低,线粒体清晰、完整,ATP值明显升高.本文的结果提示,过表达PINK1对SCA3/MJD转基因果蝇模型起保护作用,而RNA干扰PINK1表达加重SCA3/MJD转基因果蝇模型病情.PINK1在SCA3/MJD果蝇模型中的功能可能通过改善细胞内线粒体功能实现.Spinocerebellar ataxia type 3（SCA3）,also known as Machado Joseph disease（MJD）,caused by larger expanded CAG repeat sizes in the MJD1 gene,is an autosomal dominant neurodegenerative disorder of late onset. While the PINK1 protein can prevent the occurrence of Parkinson＇s disease by protecting against mitochondrial oxidative stress has been well known,its role in SCA3/MJD is unknown. To confer the protective role of PINK1 overexpression in SCA3/MJD transgenic Drosophila model,we have constructed SCA3/MJD flies,by using Mhc-Gal4 to drive the expression of MJDtr-Q78. Here,we describe the phenotypes caused by overexpression of PINK1 and RNA interference（RNAi） of PINK1 are expressed in SCA3/MJD flies respectively. Our results indicate that SCA3/MJD flies show defective wing positions,swollen mitochondria,and ATP deficits. These phenotypes could be rescued by the PINK1 overexpression but not the PINK1 RNAi. Our results suggest that overexpression of PINK1 notably protects SCA3/MJD transgenic Drosophila models,whereas PINK1 RNAi significantly aggravates SCA3/MJD transgenic Drosophila models. And this protection role of PINK1 in SCA3/MJD transgenic Drosophila models may be associated with the improvement of mitochondrial function.

关 键 词：过表达PINK1 RNA干扰PINK1 脊髓小脑性共济失调3型/马查多-约瑟夫疾病 果蝇 线粒体 

分 类 号：R74[医药卫生—神经病学与精神病学] R394[医药卫生—临床医学]