In contrast to many studies showing the pro-oxidative nature of
amyloid peptide, this work shows that aggregated Aβ42
peptide in varying concentrations (2-20 μM) in cell-free systems inhibits the formation of
hydroxyl radicals and H(2)O(2) from a mixture of
iron (20 μM FeSO(4)) and ascorbate (2mM) as measured by
benzoate hydroxylation assay and
coumarin carboxylic acid assay. Aggregated Aβ42 in similar concentrations further prevents
protein and
lipid oxidation in isolated rat brain mitochondria incubated alone or with FeSO(4) and ascorbate. Moreover, mitochondria exposed to FeSO(4) and ascorbate show enhanced formation of
reactive oxygen species and this phenomenon is also abolished by aggregated Aβ42. It is suggested that the
antioxidant property of Aβ42 in various systems is mediated by
metal chelation and it is nearly as potent as a typical
metal chelator, such as diethylenetriaminepentaacetic
acid, in preventing oxidative damage. However, aggregated Aβ42 causes mitochondrial functional impairment in the form of membrane depolarization and a loss of phosphorylation capacity without involving
reactive oxygen species in the process. Thus, the present results suggest that the
amyloid peptide exhibits a protective
antioxidant role in biological systems, but also has
toxic actions independent of oxidative stress.