title: IGF-1 reduces BACE-1 expression in PC12 cells via activation of PI3-K/Akt and MAPK/ERK1/2 signaling pathways.
abstract: Insulin-like growth factor 1 (IGF-1) stimulates α-secretase processing of amyloid precursor protein (APP) and decreases Aβ production. Little is known about the relationship between IGF-1 and β-site amyloid precursor protein cleaving enzyme 1 (BACE-1), the protease essential for the production of β-amyloid peptides (Aβ). Here, we investigated the effect of IGF-1 on BACE-1 in PC12 cells. Quantitative polymerase chain reaction analysis and western blot showed that treatment of cells with IGF-1 significantly decreased the levels of BACE-1 mRNA and protein. Furthermore, IGF-1 increased the phosphorylation of Akt and ERK1/2. The presence of the phosphatidylinositol 3-kinase (PI3-K) inhibitor LY294002 and the mitogen-activated protein kinase kinases (MEK) inhibitor PD98059 blocked the effect of IGF-1 on BACE-1. Our data indicated that IGF-1-induced reduction of BACE-1 might involve the PI3-K/Akt and MAPK/ERK1/2 signaling pathways.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Chongqing 400016, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Gao
authors.forename: Zhengwei
authors.initials: Z
authors.lastname: Dai
authors.forename: Tao
authors.initials: T
authors.lastname: Meng
authors.forename: Shengfen
authors.initials: S
authors.lastname: Tu
authors.forename: Yong
authors.initials: Y
authors.lastname: Yan
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D016716:PC12 Cells / Q000187:drug effects / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D016564:Amyloid beta-Protein Precursor; D007334:Insulin-Like Growth Factor I; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509281:Bace1 protein, rat
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