Effects of phosphatidylinositol-3 kinase/serine threonine kinase pathway on expression of beta-site amyloid precursor protein cleaving enzyme-1 in the hippocampus neurons
10.3760/cma.j.issn.1006-7876.2009.11.007
- VernacularTitle:胰岛素信号通路磷脂酰肌醇-3激酶/丝氨酸苏氨酸蛋白激酶对海马神经元β-淀粉样前体蛋白裂解酶1表达的影响
- Author:
Jieying LI
;
Yong YAN
;
Zhiyou CAI
;
Zhanhui FENG
;
Hua ZHANG
;
Fang WU
;
Tao MENG
;
Zhengwei DAI
- Publication Type:Journal Article
- Keywords:
Alzheimer disease;
Hippocampus;
1-Phosphatidylinositol 3-kinase;
Proteinserine-threonine kinases;
Aspartic endopeptidases;
Amyloid precursor protein secretases;
Insulin
- From:
Chinese Journal of Neurology
2009;42(11):737-741
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of phosphatidylinesitol-3 kinase/serine threonine kinase (PI3K/Akt) signaling pathway on expression of beta-site amyloid precursor protein cleaving enzyme-1 (BACE1) in the hippocampus neurons of rat brain. Methods Forty SD rats were randomly divided into 4 groups: blank control group, sham-operated group, insulin group and wortmannin group. Insulin or the specific inhibitor of PI3K, wortmannin was injected into hippocampus neurons to activate or inhibit the signaling pathway in insulin group or wortmannin group, respectively. Immunoprecipitation and Western blot were used to analyze the proteins levels of PI3K/Akt and BACE1. Results In insulin treatment group,among the proteins downstream of signaling pathway, expression of Akt increased (0. 952±0.060 vs 0.835±0.029,t=4.9150, P=0.0001), phospho-Akt set473 increased (0.800±0.075 vs 0.657± 0.025,t=4.5598, P=0.0002), phospho-GSK-3α decreased (0.604±0.062 vs 0.726±0.041, t= 3.5871, P=0.0018 ), and the expression of mature BACE1 and β-CTF significantly decreased. In wortmannin group, the expression of Akt and phospho-Akt ser473 were inhibited; phospho-GSK-3α increased ; mature BACEI (1.004±0.096) and β-CTF (1.031±0.048) increased (t=11.5980, P= 0.0000 and t =4.2194, P =0.0004, respectively). Conclusions PI3K/Akt signaling pathway might effect the expression of BACE1, in which impaired signaling pathway may cause the amyloid precursor protein to be easily processed by BACE1, and thus involves the pathology of Alzheimer' s disease.
