title: Interaction of NO with Cu and heme-bound Aβ peptides associated with Alzheimer's disease.
abstract: Reduced Cu and heme has been invoked to be involved in Alzheimer's disease (AD). Recently the Aβ peptides have been demonstrated to bind heme and Cu simultaneously, and this complex produces significantly more toxic partially reduced oxygen species (PROS) than the Cu or heme-bound Aβ peptides. Here a combination of absorption, EPR, and resonance Raman spectroscopy along with kinetic assays are used to investigate the interaction of nitric oxide (NO) with the physiologically relevant form of Cu and heme-bound Aβ peptides, since a down-regulation of nitric oxide synthase activity is observed in patients suffering from AD. The data indicate that NO oxidizes the Cu(I) sites, making them less toxic toward PROS generation and releases heme from the Aβ peptides ameliorating the effects of heme binding to Aβ peptides associated with AD. This process involves a tyrosine-mediated electron transfer between the Cu and heme sites. These results provide a mechanistic pathway for the possible protective role of NO in AD.
authors.affiliation: Department of Inorganic Chemistry, Indian Association for the Cultivation of Science, Kolkata, India 700032.
authors.forename: Chandradeep
authors.initials: C
authors.lastname: Ghosh
authors.forename: Debajyoti
authors.initials: D
authors.lastname: Pramanik
authors.forename: Soumya
authors.initials: S
authors.lastname: Mukherjee
authors.forename: Abhishek
authors.initials: A
authors.lastname: Dey
authors.forename: Somdatta Ghosh
authors.initials: SG
authors.lastname: Dey
mesh_terms: D000544:Alzheimer Disease; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D006418:Heme / Q000737:chemistry*; D007700:Kinetics; D009569:Nitric Oxide / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D013059:Spectrum Analysis, Raman
chemical_list: D016229:Amyloid beta-Peptides; D009569:Nitric Oxide; D006418:Heme; D003300:Copper