title: Protein "AGEing"--cytotoxicity of a glycated protein increases with its degree of AGE-modification.
abstract: Non-enzymatic glycation of proteins with reducing sugars and subsequent transition metal-catalyzed oxidations leads to the formation of protein-bound "advanced glycation endproducts" (AGEs). They accumulate on long-lived proteins including on and in the vicinity of the beta-amyloid plaques in Alzheimer's disease (AD). Since the AGE modification of a protein increases with time, and such a "long-term incubation" might also occur in the AD brain, we investigated whether an increase in the cytotoxic effects of an AGE-modified model protein occurs over time. Bovine serum albumin (BSA) was modified by glucose for defined time periods, and the viability of SH-SY5Y neuroblastoma cells, incubated with the differentially AGE-modified BSA samples, was measured with the MTT assay. Cytotoxicity of the AGE-modified BSAs increased in correlation to the incubation time with glucose. Among the AGE-specific markers, browning (OD 400) correlated best with cytotoxicity, followed by AGE-specific fluorescence and the defined AGE, carboxymethyllysine. Since AGEs accumulate in AD over time, they may be one of the "age-related" factors contributing to neuronal cell death in Alzheimer's disease.
authors.affiliation: Neuroimmunological Cell Biology, Interdisciplinary Center of Clinical Research (IZKF), Johannisallee 30a, 04103 Leipzig, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Gasic-Milenkovic
authors.forename: C
authors.initials: C
authors.lastname: Loske
authors.forename: W
authors.initials: W
authors.lastname: Deuther-Conrad
authors.forename: G
authors.initials: G
authors.lastname: Münch
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000503:physiopathology; D000818:Animals; D016922:Cellular Senescence / Q000502:physiology*; D017127:Glycation End Products, Advanced / Q000502:physiology* / Q000633:toxicity; D006801:Humans; D009447:Neuroblastoma; D009474:Neurons / Q000502:physiology; D012710:Serum Albumin, Bovine / Q000633:toxicity; D014407:Tumor Cells, Cultured / Q000502:physiology
chemical_list: D017127:Glycation End Products, Advanced; C081628:advanced glycation end products-bovine serum albumin; D012710:Serum Albumin, Bovine