淀粉样肽Aβ导致线粒体功能紊乱的体内和体外研究

被引:39
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
[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
[2] 解放军总医院骨科
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;
D O I
暂无
中图分类号
R749.16 [];
学科分类号
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.
引用
收藏
页码:154 / 160
页数:7
相关论文
共 7 条
[1]
Insights into amyloid-β-induced mitochondrial dysfunction in Alzheimer disease [J].
Wang, Xinglong ;
Su, Bo ;
Perry, George ;
Smith, Mark A. ;
Zhu, Xiongwei .
FREE RADICAL BIOLOGY AND MEDICINE, 2007, 43 (12) :1569-1573
[2]
Endogenous overproduction of β-amyloid induces tau hyperphosphorylation and decreases the solubility of tau in N2a cells [J].
Wang, Y. -P. ;
Wang, X. -C. ;
Tian, Q. ;
Yang, Y. ;
Zhang, Q. ;
Zhang, J. -Y. ;
Zhang, Y. -C. ;
Wang, Z. -F. ;
Wang, Q. ;
Li, H. ;
Wang, J. -Z .
JOURNAL OF NEURAL TRANSMISSION, 2006, 113 (11) :1723-1732
[3]
Mitochondrial abnormalities in Alzheimer brain: Mechanistic implications [J].
Bubber, P ;
Haroutunian, V ;
Fisch, G ;
Blass, JP ;
Gibson, GE .
ANNALS OF NEUROLOGY, 2005, 57 (05) :695-703
[4]
Gradual Alteration of Mitochondrial Structure and Function by β-Amyloids: Importance of Membrane Viscosity Changes; Energy Deprivation; Reactive Oxygen Species Production; and Cytochrome <Emphasis Type="Italic">c</Emphasis> Release.[J].A. M. Aleardi;G. Benard;O. Augereau;M. Malgat;J. C. Talbot;J. P. Mazat;T. Letellier;J. Dachary-Prigent;G. C. Solaini;R. Rossignol.Journal of Bioenergetics and Biomembranes.2005, 4
[5]
Protective effect of serotonin on 6-hydroxydopamine- and dopamine-induced oxidative damage of brain mitochondria and synaptosomes and PC12 cells [J].
Park, JW ;
Youn, YC ;
Kwon, OS ;
Jang, YY ;
Han, ES ;
Lee, CS .
NEUROCHEMISTRY INTERNATIONAL, 2002, 40 (03) :223-233
[6]
Molecular basis of Alzheimer's disease [J].
Drouet, B ;
Pinçon-Raymond, M ;
Chambaz, J ;
Pillot, T .
CELLULAR AND MOLECULAR LIFE SCIENCES, 2000, 57 (05) :705-715
[7]
Altered mitochondrial membrane fluidity in AD brain [J].
Mecocci, P ;
Cherubini, A ;
Beal, MF ;
Cecchetti, R ;
Chionne, F ;
Polidori, MC ;
Romano, G ;
Senin, U .
NEUROSCIENCE LETTERS, 1996, 207 (02) :129-132