1Department of Neurology, Zhongshan Hospital & Shanghai Medical College, Fudan University, Shanghai 200032, China
2State Key Laboratory of Medical Neurobiology, Institute of Brain Science, Fudan University, Shanghai 200032, China

Abstract 

Objective To determine whether high glucose enhances β-amyloid (Aβ) production in HEK293 Swedish mutant (APPsw) cells with Aβ precursor protein (APP) overexpression, and whether under this condition benfotiamine reduces the increased Aβ production. Methods HEK293 APPsw cells were cultured with different concentrations of glucose for different times. The Aβ content in the supernatant was determined by ELISA. To investigate the mechanism by which benfotiamine reduced Aβ production, glycogen synthase kinase-3 (GSK-3) activity and expression were measured after the cells were cultured with 5.5 g/L glucose for 12 h. Results With 1.0, 3.0, 4.5, 5.5, 6.5, 7.5, 8.5, or 10.5 g/L glucose, Aβproduction by HEK293 APPsw cells was highest in the presence of 5.5 g/L glucose for 6 and 12 h. The difference in Aβcontent between 5.5 and 1.0 g/L was most marked after incubation for 12 h. Benfotiamine at 20 and 40 μg/mL significantly reduced Aβ production in cells incubated with 5.5 g/L glucose for 12 h. Moreover, 40 μg/mL benfotiamine significantly enhanced the ratio of phosphorylated GSK-3 to total GSK-3, together with consistent down-regulation of GSK-3 activity. Conclusion High glucose increases Aβ production by HEK293 APPsw cells while benfotiamine prevents this increase.This is correlated with the modulation of GSK-3 activity.

Keywords

Alzheimer’s disease; β-amyloid; high glucose; benfotiamine; glycogen synthase kinase-3

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