title: Antioxidant role of amyloid β protein in cell-free and biological systems: implication for the pathogenesis of Alzheimer disease.
abstract: 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.
authors.affiliation: Department of Biochemistry, Institute of Post Graduate Medical Education & Research, Kolkata 700 020, India.
authors.forename: Maitrayee
authors.initials: M
authors.lastname: Sinha
authors.forename: Pritha
authors.initials: P
authors.lastname: Bhowmick
authors.forename: Anindita
authors.initials: A
authors.lastname: Banerjee
authors.forename: Sasanka
authors.initials: S
authors.lastname: Chakrabarti
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D002474:Cell-Free System; D008928:Mitochondria / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D017382:Reactive Oxygen Species