Phosphatidylinositol-3 Kinase/serine Threonine Kinase Signaling Pathway Influences On Expression Of Beta-site Amyloid Precursor Protein Cleaving Enzyme-1 In The Hippocampus Neurons

ObjectiveTo investigate the effect of beta-site amyloid precursor protein cleaving enzyme-1(BACE1) on phosphatidylinositol-3 kinase/serine threonine kinase (PI3K/Akt)signaling pathway in the hippocampus neurons of rat brain.MethodsInsulin and the specific inhibitor of PI3K Wortmannin were used to activate and inhibit the signaling pathway , 40 SD rats randomly divided into four group:blank control group, sham-operated group, insulin group and Wortmannin group. Immunoprecipitation and Western blot were used to analyse the proteins related to the insulin signaling and BACE1,β-CTF.ResultsThe expression of signaling pathway downstream molecules Akt and phospho-Akt ser473 were up-regulated ( P=0.000, P=0.000 ) , phospho-GSK-3αwas down-regulated(P=0.002)as well as the expression of mature BACE1 andβCTF significantly down-regulated(P=0.028,P=0.040)in insulin group. The expression of mature BACE1 andβCTF was opposite after treatment with inhibitor of PI3K(P=0.000, P=0.000), Akt and phospho-Akt ser473 were also inhibited(P=0.003,P=0.000)and phospho-GSK-3αwas increased(P=0.000). ConclusionPI3K/Akt signaling pathway might effect the expression of BACE1,which demonstrates that impaired signaling pathway shoud make the amyloid precursor protein easy to be processed by BACE1,thus to involve the pathology of Alzheimer's disease.