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

The reaction of proteins with reducing sugars leads to the formation of 'ad vanced glycation end products' (AGEs). They accumulate in Alzheimer's disea se 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 r educed glutathione in a dose- and time-dependent manner in SH-SY5Y neurobla stoma cells. The level of oxidized glutathione accounted to 10-14% and pers isted for up to 24 h in the presence of added AGEs. In contrast,the unmodif ied beta -amyloid peptides A beta (1-40) and A beta (25-35) had no signific ant effect on glutathione redox status. The AGE-induced increase in oxidize d glutathione could be prevented by the radical scavengers N-acetylcysteine , alpha -lipoic acid and 17 beta -estradiol or by application of catalase, indicating that superoxide and hydrogen peroxide production precedes the AG E-mediated depletion of reduced glutathione. (C) 2001 Elsevier Science Irel and Ltd. All rights reserved.