title: Benfotiamine prevents increased β-amyloid production in HEK cells induced by high glucose.
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, Aβ production by HEK293 APPsw cells was highest in the presence of 5.5 g/L glucose for 6 and 12 h. The difference in Aβ content 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.
  
  
  CONCLUSIONS
  High glucose increases Aβ production by HEK293 APPsw cells while benfotiamine prevents this increase. This is correlated with the modulation of GSK-3 activity.
authors.affiliation: Department of Neurology, Zhongshan Hospital & Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Sun
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.forename: Na
authors.initials: N
authors.lastname: Zhao
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Pan
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Fei
authors.forename: Li-Rong
authors.initials: LR
authors.lastname: Jin
authors.forename: Chun-Jiu
authors.initials: CJ
authors.lastname: Zhong
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000008:administration & dosage* / Q000633:toxicity*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D057809:HEK293 Cells; D006801:Humans; D013831:Thiamine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D016229:Amyloid beta-Peptides; D038362:Glycogen Synthase Kinase 3; D005947:Glucose; D013831:Thiamine; C013835:benphothiamine