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γ-Glutamylcysteine ethyl ester protection of proteins from Aβ(1–42)-mediated oxidative stress in neuronal cell culture: A proteomics approach

Authors

  • Debra Boyd-Kimball,

    1. Department of Chemistry, Center for Membrane Sciences, University of Kentucky, Lexington, Kentucky
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  • Rukhsana Sultana,

    1. Department of Chemistry, Center for Membrane Sciences, University of Kentucky, Lexington, Kentucky
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  • H. Fai Poon,

    1. Department of Chemistry, Center for Membrane Sciences, University of Kentucky, Lexington, Kentucky
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  • Hafiz Mohmmad-Abdul,

    1. Department of Chemistry, Center for Membrane Sciences, University of Kentucky, Lexington, Kentucky
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  • Bert C. Lynn,

    1. Department of Chemistry, Center for Membrane Sciences, University of Kentucky, Lexington, Kentucky
    2. Core Proteomics Laboratory, University of Kentucky, Lexington, Kentucky
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  • Jon B. Klein,

    1. Kidney Disease Program and Proteomics Core Laboratory, University of Louisville School of Medicine and VAMC, Louisville, Kentucky
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  • D. Allan Butterfield

    Corresponding author
    1. Department of Chemistry, Center for Membrane Sciences, University of Kentucky, Lexington, Kentucky
    2. Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky
    • Department of Chemistry, Center for Membrane Sciences, and Sanders-Brown Center on Aging, 121 Chemistry-Physics Building, University of Kentucky, Lexington, KY 40506-0055
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Abstract

Protein oxidation mediated by amyloid β-peptide (1–42) (Aβ[1–42]) has been proposed to play a central role in the pathogenesis of Alzheimer's disease (AD), a neurodegenerative disorder associated with aging and the loss of cognitive function. The specific mechanism by which Aβ(1–42), the primary component of the senile plaque and a pathologic hallmark of AD, contributes to the oxidative damage evident in AD brain is unknown. Moreover, the specific proteins that are vulnerable to oxidative damage induced by Aβ(1–42) are unknown. Identification of such proteins could contribute to our understanding of not only the role of Aβ(1–42) in the pathogenesis of AD, but also provide insight into the mechanisms of neurodegeneration at the protein level in AD. We report the proteomic identification of two proteins found to be oxidized significantly in neuronal cultures treated with Aβ(1–42): 14-3-3ζ and glyceraldehyde-3-phosphate dehydrogenase. We also report that pretreatment of neuronal cultures with γ-glutamylcysteine ethyl ester, a compound that supplies the limiting substrate for the synthesis of glutathione and results in the upregulation of glutathione in neuronal cultures, protects both proteins against Aβ(1–42)-mediated protein oxidation. © 2005 Wiley-Liss, Inc.

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