Involvement of oxidative stress in the enhancement of acetylcholinesterase acti...

• Author(s): Melo, Joana Barbosa ; Agostinho, Paula ; Oliveira, Catarina Resende
• Date: 2003
• Persistent ID: http://hdl.handle.net/10316/4817
• Origin: Estudo Geral - Universidade de Coimbra
• Subject(s): Acetylcholinesterase; Beta-amyloid; Oxidative stress; Nitric oxide synthase; Retinal cells
• Document Type: Article
• Language: English

Description

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 A[beta]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 A[beta]25-35 (25 [mu]M, 24 h) and antioxidants such as [alpha]-tocopherol acetate and nitric oxide synthase (NOS) inhibitors were capable of preventing this effect. Despite A[beta]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 A[beta]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. http://www.sciencedirect.com/science/article/B6T0H-47GJ2R1-9/1/a97240b0c572732e7101ea21ffee49da