Involvement of oxidative stress in the enhancement of acetylcholinesterase activity induced by amyloid beta-peptide.
Acetylcholinesterase (AChE) activity is increased within and around amyloid plaques, which are present in Alzheimer's disease (AD) patient's brain. In this study, using cultured retinal cells as a neuronal model, we analyzed the effect of the synthetic peptide Abeta(25-35) on the activity of AChE, the degradation enzyme of acetylcholine, as well as the involvement of oxidative stress in this process. The activity of AChE was increased when retinal cells were incubated with Abeta(25-35) (25 microM, 24 h) and antioxidants such as alpha-tocopherol acetate and nitric oxide synthase (NOS) inhibitors were capable of preventing this effect. Despite Abeta(25-35) did not affect cell membrane integrity, the redox capacity of cells decreased. The incubation with this amyloidogenic peptide led to an increment of reactive oxygen species formation (20%), of lipid peroxidation (65%), and basal intracellular calcium levels (40%). The data obtained show that the enhancement of AChE activity induced by Abeta(25-35) is mediated by oxidative stress, and that vitamin E and NOS inhibitors, by preventing the compromise of the enzyme activity, can have an important role in the maintenance of acetylcholine synaptic levels, thus preventing or improving cognitive and memory functions of AD patients.
Melo
Joana Barbosa
JB
Center for Neurosciences of Coimbra and Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal.
Agostinho
Paula
P
Oliveira
Catarina Resende
CR
D000110:Acetylcholinesterase / Q000187:drug effects / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002642:Chick Embryo; D015227:Lipid Peroxidation / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012160:Retina / Q000187:drug effects / Q000378:metabolism
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D017382:Reactive Oxygen Species; D000110:Acetylcholinesterase; D002118:Calcium