胰岛素样生长因子-1对β-淀粉样前体蛋白裂解酶1的影响

被引：2

作者：

谭家泽 ^{[1
]}

宦小芳 ^{[2
]}

机构：

[1] 重庆医科大学附属第一医院神经内科

[2] 重庆市石柱县人民医院护理部

来源：

重庆医科大学学报 | 2013年 / 38卷 / 09期

关键词：

胰岛素样生长因子-1; β-淀粉样前体蛋白裂解酶1; 磷脂酰肌醇-3激酶; 丝氨酸苏氨酸蛋白激酶;

D O I：

暂无

中图分类号：

R749.16 [];

学科分类号：

100203 ;

摘要：

目的:探讨胰岛素样生长因子-1(insulin-like growth factor-1,IGF-1)对人类神经母细胞瘤细胞SH-SY5Y中β-淀粉样前体蛋白裂解酶1(β-site amyloid precursor protein cleaving enzyme1,BACE1)的影响以及可能的细胞信号机制。方法:用不同剂量IGF-1(20、40 ng/ml和80 ng/ml)作用于人类神经母细胞瘤细胞SH-SY5Y 24 h,荧光定量PCR及Western blot检测BACE-1mRNA及蛋白水平;Western blot检测淀粉样前体蛋白、C99、C83及磷脂酰肌醇-3激酶/丝氨酸苏氨酸蛋白激酶(phosphoinositide3-kinase/serine threonine kinase,PI3-K/Akt)通路相关蛋白的水平;ELISA检测细胞培养液中β-淀粉样蛋白42(β-amyloid peptide,Aβ42)的水平,然后选择最佳剂量的IGF-1(80 ng/ml)作用于人类神经母细胞瘤细胞SH-SY5Y,在此之前30 min加入PI3-K抑制剂LY294002(25μmol/L及50μmol/L),重复上述检测。结果:IGF-1降低BACE-1、C99及Aβ42的水平(P=0.000),提高C83的表达(P=0.000),增加Akt的磷酸化(P=0.000),而LY294002具有抑制IGF-1的上述作用。结论:IGF-1降低BACE-1mRNA及蛋白的水平,其机制可能涉及PI3-K/Akt信号通路。

引用

页码：979 / 983

页数：5

共 10 条

[1] Rapid P1 SAR of brain penetrant tertiary carbinamine derived BACE inhibitors [J].

Zhu, Hong ;

Young, Mary B. ;

Nantermet, Philippe G. ;

Graham, Samuel L. ;

Colussi, Dennis ;

Lai, Ming-Tain ;

Pietrak, Beth ;

Price, Eric A. ;

Sankaranarayanan, Sethu ;

Shi, Xiao-ping ;

Tugusheva, Katherine ;

Holahan, Marie A. ;

Michener, Maria S. ;

Cook, Jacquelynn J. ;

Simon, Adam ;

Hazuda, Daria J. ;

Vacca, Joseph P. ;

Rajapakse, Hemaka A. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (05) :1779-1782

[2]

Biological markers of amyloid β-related mechanisms in Alzheimer's disease[J] . Harald Hampel,Yong Shen,Dominic M. Walsh,Paul Aisen,Les M. Shaw,Henrik Zetterberg,John Q. Trojanowski,Kaj Blennow. Experimental Neurology . 2009 (2)

[3] Measurement of cellular β-site of APP cleaving enzyme 1 activity and its modulation in neuronal assay systems [J].

Volbracht, Christiane ;

Penzkofer, Stephan ;

Mansson, David ;

Christensen, Kenneth Vielsted ;

Fog, Karina ;

Schildknecht, Stefan ;

Leist, Marcel ;

Nielsen, Jacob .

ANALYTICAL BIOCHEMISTRY, 2009, 387 (02) :208-220

[4]

Amyloid β and APP as biomarkers for Alzheimer’s disease[J] . Henrik Zetterberg,Kaj Blennow,Eric Hanse. Experimental Gerontology . 2009 (1)

[5]

The amyloid precursor protein intracellular domain (AICD) as modulator of gene expression, apoptosis, and cytoskeletal dynamics—Relevance for Alzheimer's disease[J] . Thorsten Müller,Helmut E. Meyer,Rupert Egensperger,Katrin Marcus. Progress in Neurobiology . 2008 (4)

[6] Relationship between serum insulin-like growth factor-1 levels and Alzheimer's disease and vascular dementia [J].

Watanabe, T ;

Miyazaki, A ;

Katagiri, T ;

Yamamoto, H ;

Idei, T ;

Iguchi, T .

JOURNAL OF THE AMERICAN GERIATRICS SOCIETY, 2005, 53 (10) :1748-1753

[7]

Beta-site APP cleaving enzyme 1 (BACE1) is increased in remaining neurons in Alzheimer's disease brains[J] . Hirotsugu Harada,Akira Tamaoka,Kazuhiro Ishii,Shin’ichi Shoji,Satoshi Kametaka,Fuyuki Kametani,Yuko Saito,Shigeo Murayama. Neuroscience Research . 2005 (1)

[8]

The role of insulin and insulin-like growth factor I in the molecular and cellular mechanisms underlying the pathology of Alzheimer's disease[J] . Eva Carro,Ignacio Torres-Aleman. European Journal of Pharmacology . 2004 (1)

[9] BACE1 deficiency rescues memory deficits and cholinergic dysfunction in a mouse model of Alzheimer's disease [J].

Ohno, M ;

Sametsky, EA ;

Younkin, LH ;

Oakley, H ;

Younkin, SG ;

Citron, M ;

Vassar, R ;

Disterhoft, JF .

NEURON, 2004, 41 (01) :27-33

[10] Clearing the brain's amyloid cobwebs [J].

Selkoe, DJ .

NEURON, 2001, 32 (02) :177-180

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