Advanced glycation endproducts cause lipid peroxidation in the human neuronal cell line SH-SY5Y.
Advanced glycation endproducts (AGEs), sugar-derived protein modifications and lipid peroxidation products are prominent features of Alzheimer's disease. AGEs accumulate on beta-amyloid plaques during the course of the disease and can exert chronic oxidative stress via receptor-mediated mechanisms. Lipid peroxidation products such as hydroxynonenal, further markers of oxidative stress, are also increased in Alzheimer's diesease. In this study we present evidence for a direct biochemical link between AGEs and lipid peroxidation. Our results show that AGEs induce lipid peroxidation in a neuronal cell line in a dose-dependant manner, and that blocking the specific AGE-receptor RAGE, as well as using different antioxidants (alpha-lipoic acid, N-acetylcysteine, 17 beta-estradiol or aminoguanidine) can reduce the AGE-mediated formation of lipid peroxidation products. Thus, both RAGE antagonists and scavengers of oxygen free radicals could be useful in protecting brain tissue from lipid peroxidation and its pathophysilogical consequences that occur in Alzheimer's disease.
Gasic-Milenkovic
Jovana
J
Neuroimmunological Cell Biology Unit, Interdisciplinary Center for Clinical Research (IZKF) Leipzig, Germany.
Loske
Claudia
C
Münch
Gerald
G
D000111:Acetylcysteine / Q000494:pharmacology*; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology*; D005609:Free Radicals / Q000037:antagonists & inhibitors; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D008063:Thioctic Acid / Q000494:pharmacology*
D005609:Free Radicals; D017127:Glycation End Products, Advanced; D004958:Estradiol; D008063:Thioctic Acid; D000111:Acetylcysteine