title: Interaction of superoxide dismutase with the glycine zipper regions of β-amyloid peptides: is there an implication towards Alzheimer's disease and oxidative stress?
abstract: Not only are β-amyloid peptides and senile plaque deposits characteristics in Alzheimer's disease but there is growing evidence to suggest that oxidative stress also plays a role with a decrease in levels of brain superoxide dismutase (SOD), an enzyme that catalyses the dismutation of superoxide radicals into molecular oxygen and hydrogen peroxide. We show through kinetic and fluorescence analysis that β-amyloid peptides, in the glycine zipper region [Aβ₂₉₋₃₃ and Aβ₂₅₋₃₇] of Aβ₁₋₄₀ interact with, and inhibit, SOD directly. The enzyme was purified 15.7-fold from bovine brain by DEAE-Sepharose ion exchange chromatography in a yield of 68.8% and specific activity of 3.66 U.mg(-1). The subunit structure of the enzyme was monomeric with a molecular mass of 13 kDa, as estimated by SDS-PAGE. Inhibitor constants (Ki) and dissociation constants (Kd) were calculated as 14.44, 13.16 and 11.72 µM and 9.38, 15.7 and 12.13 for Aβ₂₅₋₃₇, Aβ₂₉₋₃₃ and Aβ₁₋₄₀, respectively; the number of binding sites on the enzyme for the peptides was 1.
authors.affiliation: Department of Biochemistry, Microbiology & Biotechnology, Rhodes University, Grahamstown, South Africa.
authors.forename: F
authors.initials: F
authors.lastname: Oyatsi
authors.forename: C G
authors.initials: CG
authors.lastname: Whiteley
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000201:enzymology; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D005998:Glycine / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D018384:Oxidative Stress / Q000187:drug effects*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D013482:Superoxide Dismutase; D005998:Glycine