title: Vitamin B6s inhibit oxidative stress caused by Alzheimer's disease-related Cu(II)-β-amyloid complexes-cooperative action of phospho-moiety.
abstract: Cu(II) complexes of Alzheimer's disease-related β-amyloid (Aβ) peptides exhibit metal-centered oxidation chemistry. The metallo-Aβ complexes are the hallmark of the disease and have been attributed to the generation of reactive oxygen species (ROS), causing oxidative stress. In this communication, the inhibitions of the oxidative activity of Cu(II)-Aβ by vitamin B6 compounds pyridoxamine (PM), pyridoxine (PN), pyridoxal (PL), and pyridoxal-5'-phosphate (PLP) are presented. These B6's are competitive inhibitors toward dopamine oxidation by Cu(II)-Aβ(1-20), with K(i) values of 1.4, 8.3, 1.2, and 0.2mM, respectively. The phospho-moiety in PLP seems to exhibit cooperative inhibition, affording a clue for future design of inhibitors.
authors.affiliation: Department of Chemistry, University of South Florida, 4202 E Fowler Ave., Tampa, FL 33612, USA.
authors.forename: Alaa
authors.initials: A
authors.lastname: Hashim
authors.forename: Le
authors.initials: L
authors.lastname: Wang
authors.forename: Kashmir
authors.initials: K
authors.lastname: Juneja
authors.forename: Yong
authors.initials: Y
authors.lastname: Ye
authors.forename: Yufen
authors.initials: Y
authors.lastname: Zhao
authors.forename: Li-June
authors.initials: LJ
authors.lastname: Ming
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D003300:Copper / Q000378:metabolism*; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D025101:Vitamin B 6 / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D017382:Reactive Oxygen Species; D003300:Copper; D025101:Vitamin B 6