Effects of insulin-like growth factor 1 on β-site amyloid precursor protein cleaving enzyme1

Abstract:

Objective：To observe the effects of insulin-like growth factor-1（IGF-1） on β-site amyloid precursor protein cleaving en－zyme1（BACE1） and the possible cellular signaling mechanisms in SH-SY5Y human neuroblastoma cells. Methods：After SH-SY5Y human neuroblastoma cells being treated with 20，40 ng/ml and 80 ng/ml IGF-1 for 24 h，qPCR was used to analyze the levels of BACE-1 and Western blot was used to detect the protein levels of BACE1，C99，C83，amyloid precursor protein，mRNA and related protein levels of phosphoinositide 3-kinase/serine threonine kinase（PI3-K/Akt）. Cellular culture medium levels of β-amyloid pep－tide（Aβ42） were analyzed by ELISA. For inhibition studies，25 μmol/L and 50 μmol/L LY 294002，a specific PI3-K inhibitor，was administered 30 min prior to 80 ng/ml IGF-1 treatment. Then the above tests were repeated. Results：IGF-1 decreased levels of BACE-1，C99，and Aβ42（P=0.000） and increased expressions of C83 and pAkt（P=0.000）. LY294002 inhibited the above effects of IGF-1. Conclusion：IGF-1-induced reduction of BACE-1 may involve in PI3-K/Akt signaling pathway.