IGF-1 Reduces BACE-1 Expression in PC12 Cells via Activation of PI3-K/Akt and MAPK/ERK1/2 Signaling Pathways

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-...

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Bibliographic Details
Published in:Neurochemical research 2011, Vol.36 (1), p.49-57
Main Authors: Zhang, Hua, Gao, Ying, Dai, Zhengwei, Meng, Tao, Tu, Shengfen, Yan, Yong
Format: Article
Language:English
Subjects:
Amyloid beta-Protein Precursor - genetics
Amyloid beta-Protein Precursor - metabolism
Amyloid Precursor Protein Secretases - genetics
Amyloid Precursor Protein Secretases - metabolism
Animals
Aspartic Acid Endopeptidases - genetics
Aspartic Acid Endopeptidases - metabolism
Biochemistry
Biomedical and Life Sciences
Biomedicine
Cell Biology
Enzyme Activation
Insulin-Like Growth Factor I - pharmacology
Mitogen-Activated Protein Kinase 1 - metabolism
Mitogen-Activated Protein Kinase 3 - metabolism
Neurochemistry
Neurology
Neurosciences
Original Paper
PC12 Cells - drug effects
PC12 Cells - metabolism
Phosphatidylinositol 3-Kinase - metabolism
Proto-Oncogene Proteins c-akt - metabolism
Rats
Signal Transduction - drug effects
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Summary: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.
ISSN:0364-3190
1573-6903
DOI:10.1007/s11064-010-0260-x