淀粉样肽Aβ导致线粒体功能紊乱的体内和体外研究  

Research on The Effect of Amyloid beta on Mitochondrial Dysfunction In vivo and In vitro

作　　者：刘玲玲[1] 盛柏杨[1] 龚锴[1] 赵南明[1] 张秀芳[1] 唐佩福[2] 公衍道[1] 

机构地区：[1]清华大学生命科学学院,生物膜与膜生物工程国家重点实验室,北京100084 [2]解放军总医院骨科,北京100853

出　　处：《生物化学与生物物理进展》2010年第2期154-160,共7页Progress In Biochemistry and Biophysics

基　　金：清华裕元医学科学研究基金(20240000514);生物膜与膜生物工程国家重点实验室基金;国家自然科学基金(30973068);国家高技术研究发展计划(863)(2008AA022403)资助项目~~

摘　　要：为探索阿尔茨海默症(AD)中β淀粉样肽(Aβ)对线粒体功能的影响,比较了稳定表达人野生型淀粉样前体蛋白(APP)的细胞和同时转入人Swedish突变APP及ΔE9突变PS1的双转细胞(swe.Δ9)的线粒体功能.结果发现,swe.Δ9细胞的线粒体膜电位、细胞色素c氧化酶活性、线粒体膜流动性、ATP含量均明显低于APP细胞,而APP细胞又明显低于对照的转入空质粒的细胞.在转基因小鼠上也得到类似结果:同时转入人Swedish突变APP和人PS1 M146V敲入的双转小鼠的细胞色素c氧化酶活性和ATP含量比只转入Swedish突变APP的Tg2576小鼠更低.结果证明了AD模型中线粒体功能损害程度与Aβ产量的正相关关系.To investigate the effect of Aβ on mitochondrial dysfunction,cells stably transfected by human amyloid precursor protein 695（APP） and cells stably co-transfected by familial Alzheimer＇s disease（FAD）-linked Swedish mutant of APP695 gene plus ΔE9 deleted presenilin1 gene（swe.Δ9）were used to study the mitochondrial function.Swe.Δ9 cells showed more reduce in mitochondrial membrane potential,altered complex Ⅳ activity,mitochondrial membrane fluidity and ATP content.However,these parameters in APP cells were lower than those in N2a cells stably transfected with empty vector.The similar results were observed in transgenic mice.APP/PS1M146V/＋ mice showed more reduced complex Ⅳ activity and ATP content than Tg2576 mice.These data indicated that the dose-dependent effect of Aβ on mitochondrial dysfunction.

关 键 词：阿尔茨海默症 线粒体 Β淀粉样蛋白 线粒体膜电位 细胞色素c氧化酶活性 线粒体膜流动性 ATP 

分 类 号：Q6[生物学—生物物理学] R338[医药卫生—人体生理学]