title: Purported Interactions of Amyloid-β and Glucocorticoids in Cytotoxicity and Genotoxicity: Implications in Alzheimer's Disease.
abstract: Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by the presence of aggregates of the amyloid-β peptide (Aβ) that are believed to be neurotoxic. One of the purposed damaging mechanisms of Aβ is oxidative insult, which eventually could damage the cellular genome. Stress and associated increases in glucocorticoids (GCs) have been described as a risk factor for the development of AD, although the purported genotoxic effects of GCs have not been fully characterized. Therefore, it is possible to speculate about purported synergistic effects of GCs on the Aβ-driven genotoxic damage. This in vitro study addresses the single and combined cyto/genotoxic effects of Aβ and GCs in SH-SY5Y cells. Cytotoxicity was determined by the MTT assay, and the genotoxic effects were studied using the comet assay. A comet assay derivation allows for measuring the presence of the FPG-sensitive sites (mainly 8-oxoguanines) in the DNA, apart from the DNA strand breaks. Treatment with Aβ (10 μM, 72 h) induced cytotoxicity (35% decrease in cell viability) and DNA strand breaks, but had no significant effect on oxidative DNA damage (FPG sites). Corticosterone showed no effect on cell viability, genotoxicity, or reparation processes. Corticosterone was unable to neither reverse nor potentiate Aβ driven effects. The present results suggest the existence of alternative mechanisms for the Aβ driven damage, not involving oxidative damage of DNA. In addition, could be suggested that the interaction between Aβ and GCs in AD does not seem to involve DNA damage.
authors: Xabier
authors: X
authors: Bengoetxea
authors: Adela López
authors: AL
authors: de Cerain
authors: Amaya
authors: A
authors: Azqueta
authors: Maria J
authors: MJ
authors: Ramirez
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000633:toxicity*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003603:Cytotoxins / Q000378:metabolism / Q000633:toxicity*; D004249:DNA Damage / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D005938:Glucocorticoids / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D010446:Peptide Fragments / Q000378:metabolism / Q000633:toxicity*
chemical_list: D016229:Amyloid beta-Peptides; D003603:Cytotoxins; D005938:Glucocorticoids; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35)
keywords: Comet assay; DNA breaks; DNA damage; DNA-formamidopyrimidine glycosylase; oxidative stress