title: Protective effect of D609 against amyloid-beta1-42-induced oxidative modification of neuronal proteins: redox proteomics study.
abstract: Oxidative stress has been implicated in the pathophysiology of a number of diseases, including neurodegenerative disorders such as Alzheimer's disease (AD), a neurodegenerative disorder associated with cognitive decline and enhanced oxidative stress. Amyloid-beta peptide(1-42) (Abeta(1-42)), one of the main component of senile plaques, can induce in vitro and in vivo oxidative damage to neuronal cells through its ability to produce free radicals. The aim of this study was to investigate the protective effect of the xanthate D609 on Abeta(1-42)-induced protein oxidation by using a redox proteomics approach. D609 was recently found to be a free radical scavenger and antioxidant. In the present study, rat primary neuronal cells were pretreated with 50 microM of D609, followed by incubation with 10 microM Abeta(1-42) for 24 hr. In the cells treated with Abeta(1-42) alone, four proteins that were significantly oxidized were identified: glyceraldehyde-3-phosphate dehydrogenase, pyruvate kinase, malate dehydrogenase, and 14-3-3 zeta. Pretreatment of neuronal cultures with D609 prior to Abeta(1-42) protected all the identified oxidized proteins in the present study against Abeta(1-42)-mediated protein oxidation. Therefore, D609 may ameliorate the Abeta(1-42)-induced oxidative modification. We discuss the implications of these Abeta(1-42)-mediated oxidatively modified proteins for AD pathology and for potential therapeutic intervention in this dementing disorder.
authors.affiliation: Department of Chemistry, University of Kentucky, Lexington, 40506, USA.
authors.forename: Rukhsana
authors.initials: R
authors.lastname: Sultana
authors.forename: Shelley F
authors.initials: SF
authors.lastname: Newman
authors.forename: Hafiz Mohmmad
authors.initials: HM
authors.lastname: Abdul
authors.forename: Jian
authors.initials: J
authors.lastname: Cai
authors.forename: William M
authors.initials: WM
authors.lastname: Pierce
authors.forename: Jon B
authors.initials: JB
authors.lastname: Klein
authors.forename: Michael
authors.initials: M
authors.lastname: Merchant
authors.forename: D Allan
authors.initials: DA
authors.lastname: Butterfield
mesh_terms: D048948:14-3-3 Proteins / Q000187:drug effects / Q000378:metabolism; D000544:Alzheimer Disease / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D002478:Cells, Cultured; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000187:drug effects / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D008291:Malate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D013058:Mass Spectrometry; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009636:Norbornanes; D010084:Oxidation-Reduction / Q000187:drug effects; D050050:Protein Carbonylation / Q000187:drug effects; D040901:Proteomics; D011770:Pyruvate Kinase / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology*
chemical_list: D048948:14-3-3 Proteins; D016229:Amyloid beta-Peptides; D001952:Bridged-Ring Compounds; D018696:Neuroprotective Agents; D009636:Norbornanes; D013859:Thiocarbamates; D013871:Thiones; C046498:tricyclodecane-9-yl-xanthogenate; D008291:Malate Dehydrogenase; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D011770:Pyruvate Kinase