title: Copper ions influence the toxicity of β-amyloid(1-42) in a concentration-dependent manner in a Caenorhabditis elegans model of Alzheimer's disease.
abstract: β-amyloid (Aβ) and copper play important roles in the pathogenesis of Alzheimer's disease (AD). However, the behavioral correlativity and molecular mechanisms of Aβ and copper toxicity have been investigated less often. In the present study, we investigated the interaction and toxicity of Aβ1-42 and copper in the Aβ1-42 transgenic Caenorhabditis elegans worm model CL2006. Our data show that the paralysis behavior of CL2006 worms significantly deteriorated after exposure to 10(-3) mol L(-1) copper ions. However, the paralysis behavior was dramatically attenuated with exposure to 10(-4) mol L(-1) copper ions. The exogenous copper treatment also partially changed the homeostatic balance of zinc, manganese, and iron. Our data suggest that the accumulation of reactive oxygen species (ROS) was responsible for the paralysis induced by Aβ and copper in CL2006. The ROS generation induced by Aβ and copper appear to be through sod-1, prdx-2, skn-1, hsp-60 and hsp-16.2 genes.
authors.affiliation: State Key Laboratory of Brain & Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: YunFeng
authors.initials: Y
authors.lastname: Luo
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: NianQing
authors.initials: N
authors.lastname: Liu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Luo
authors.forename: BaoLu
authors.initials: B
authors.lastname: Zhao
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D003300:Copper / Q000378:metabolism / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D006706:Homeostasis; D007477:Ions / Q000378:metabolism / Q000633:toxicity*; D018384:Oxidative Stress; D010243:Paralysis / Q000139:chemically induced; D010446:Peptide Fragments / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000633:toxicity; D017356:Synchrotrons
chemical_list: D016229:Amyloid beta-Peptides; D029742:Caenorhabditis elegans Proteins; D007477:Ions; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C075222:amyloid beta-protein (1-42); D003300:Copper