Protective effect of D609 against amyloid-beta1-42-induced oxidative modification of neuronal proteins: Redox proteomics study

Rukhsana Sultana, Shelley F. Newman, Hafiz Mohmmad Abdul, Jian Cai, William M. Pierce, Jon B. Klein, Michael Merchant, D. Allan Butterfield

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

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 peptide1-42 (Aβ1-42), 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 Aβ1-42-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 μM of D609, followed by incubation with 10 μM Aβ1-42 for 24 hr. In the cells treated with Aβ1-42 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 Aβ1-42 protected all the identified oxidized proteins in the present study against Aβ1-42-mediated protein oxidation. Therefore, D609 may ameliorate the Aβ1-42-induced oxidative modification. We discuss the implications of these Aβ1-42-mediated oxidatively modified proteins for AD pathology and for potential therapeutic intervention in this dementing disorder.

Original languageEnglish
Pages (from-to)409-417
Number of pages9
JournalJournal of Neuroscience Research
Volume84
Issue number2
DOIs
StatePublished - Aug 1 2006

Keywords

  • Alzheimer's disease
  • Oxidative stress
  • Protein carbonyls
  • Redox proteomics

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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