title: Tripeptide GGH as the Inhibitor of Copper-Amyloid-β-Mediated Redox Reaction and Toxicity.
abstract: The Aβ complexes of some redox-active species, such as Cu, cause oxidative stress and induce severe toxicity by generating reactive oxygen species (ROS). Thus, Cu chelation therapy should be considered as a valuable strategy for the treatment of Alzheimer's disease (AD). However, more attention should be paid to the specific chelating ability of these chelating agents. Herein, a tripeptide GGH was used to selectively chelate the Cu(2+) in Aβ-Cu complex in the presence of other metal ions (e.g., K(+), Ca(2+), Ni(2+), Mg(2+), and Zn(2+)) as shown by isothermal titration calorimetry results. GGH decreased the level of HO(•) radicals by preventing the formation of intermediate Cu(I) ion. Thus, the Cu species completely lost its catalytic activity at a superequimolar GGH/Cu(II) ratio (4:1) as observed by UV-visible spectroscopy, coumarin-3-carboxylic acid fluorescence, and BCA assay. Moreover, (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay indicates that GGH increased PC-12 cell viability from 36% to 63%, and neurotoxicity partly triggered by ROS decreased. These results indicate potential development of peptide chelation therapy for AD treatment.
authors.affiliation: Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, Nankai University , Tianjin 300071, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Hu
authors.affiliation: Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, Nankai University , Tianjin 300071, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, Nankai University , Tianjin 300071, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, Nankai University , Tianjin 300071, China.|Collaborative Innovation Center of Chemical Science and Engineering (Tianjin) , Tianjin 300071, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yuan
authors.affiliation: Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, Nankai University , Tianjin 300071, China.
authors.forename: Xushan
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, Nankai University , Tianjin 300071, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Chen
authors.affiliation: Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, Nankai University , Tianjin 300071, China.
authors.forename: Xingyu
authors.initials: X
authors.lastname: Chen
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002614:Chelating Agents / Q000737:chemistry / Q000494:pharmacology*; D003300:Copper / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008670:Metals / Q000378:metabolism / Q000494:pharmacology; D046529:Microscopy, Electron, Transmission; D009474:Neurons / Q000187:drug effects; D009842:Oligopeptides / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells / Q000187:drug effects* / Q000648:ultrastructure; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D002614:Chelating Agents; D008670:Metals; D009842:Oligopeptides; D017382:Reactive Oxygen Species; C037026:diglycyl-histidine; D003300:Copper
keywords: Alzheimer’s disease; Cu ion; amyloid-β peptide; peptide chelator