Advanced glycation endproducts change glutathione redox status in SH-SY5Y human neuroblastoma cells by a hydrogen peroxide dependent mechanism

Neurosci Lett. 2001 Oct 12;312(1):29-32. doi: 10.1016/s0304-3940(01)02174-7.


The reaction of proteins with reducing sugars leads to the formation of 'advanced glycation endproducts' (AGEs). They accumulate in Alzheimer's disease brain in the vicinity of beta-amyloid plaques. AGEs are cytotoxic by a mechanism involving reactive oxygen species, which implies that they could compromise glutathione redox status. In this study, we show that AGEs (BSA-AGE and beta-amyloid-AGE) persistently increase the ratio of oxidized to reduced glutathione in a dose- and time-dependent manner in SH-SY5Y neuroblastoma cells. The level of oxidized glutathione accounted to 10-14% and persisted for up to 24 h in the presence of added AGEs. In contrast, the unmodified beta-amyloid peptides A beta (1-40) and A beta (25-35) had no significant effect on glutathione redox status. The AGE-induced increase in oxidized glutathione could be prevented by the radical scavengers N-acetylcysteine, alpha-lipoic acid and 17beta-estradiol or by application of catalase, indicating that superoxide and hydrogen peroxide production precedes the AGE-mediated depletion of reduced glutathione.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides / pharmacology
  • Antioxidants / pharmacology
  • Brain / metabolism*
  • Brain / physiopathology
  • Glutathione / drug effects
  • Glutathione / metabolism*
  • Glycation End Products, Advanced / metabolism*
  • Glycation End Products, Advanced / pharmacology
  • Humans
  • Hydrogen Peroxide / metabolism*
  • Neurons / metabolism*
  • Neuroprotective Agents / pharmacology
  • Oxidation-Reduction
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology
  • Peptide Fragments / pharmacology
  • Serum Albumin, Bovine / pharmacology
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / metabolism


  • Amyloid beta-Peptides
  • Antioxidants
  • Glycation End Products, Advanced
  • Neuroprotective Agents
  • Peptide Fragments
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (25-35)
  • Serum Albumin, Bovine
  • Hydrogen Peroxide
  • Glutathione