title: Advanced glycation endproducts change glutathione redox status in SH-SY5Y human neuroblastoma cells by a hydrogen peroxide dependent mechanism.
abstract: 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.
authors.affiliation: Neuroimmunological Cell Biology, Interdisciplinary Center of Clinical Research (IZKF) Leipzig, Johannisallee 30a, 04103 Leipzig, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Deuther-Conrad
authors.forename: C
authors.initials: C
authors.lastname: Loske
authors.forename: R
authors.initials: R
authors.lastname: Schinzel
authors.forename: R
authors.initials: R
authors.lastname: Dringen
authors.forename: P
authors.initials: P
authors.lastname: Riederer
authors.forename: G
authors.initials: G
authors.lastname: Münch
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D017127:Glycation End Products, Advanced; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C074636:amyloid beta-protein (25-35); D012710:Serum Albumin, Bovine; D006861:Hydrogen Peroxide; D005978:Glutathione