Plasma proteomic alterations in non-human primates and humans after chronic alcohol self-administration

Willard M. Freeman, Heather D. Vanguilder, Elizabeth Guidone, John H. Krystal, Kathleen (Kathy) Grant, Kent E. Vrana

    Research output: Contribution to journalArticle

    9 Citations (Scopus)

    Abstract

    Objective diagnostics of excessive alcohol use are valuable tools in the identification and monitoring of subjects with alcohol use disorders. A number of potential biomarkers of alcohol intake have been proposed, but none have reached widespread clinical usage, often due to limited diagnostic sensitivity and specificity. In order to identify novel potential biomarkers, we performed proteomic biomarker target discovery in plasma samples from non-human primates that chronically self-administer high levels of ethanol. Two-dimensional difference in-gel electrophoresis (2D-DIGE) was used to quantify plasma proteins from within-subject samples collected before exposure to ethanol and after 3 months of excessive ethanol self-administration. Highly abundant plasma proteins were depleted from plasma samples to increase proteomic coverage. Altered plasma levels of serum amyloid A4 (SAA4), retinol-binding protein, inter-alpha inhibitor H4, clusterin, and fibronectin, identified by 2D-DIGE analysis, were confirmed in unmanipulated, whole plasma from these animals by immunoblotting. Examination of these target plasma proteins in human subjects with excessive alcohol consumption (and control subjects) revealed increased levels of SAA4 and clusterin and decreased levels of fibronectin compared to controls. These proteins not only serve as targets for further development as biomarker candidates or components of biomarker panels, but also add to the growing understanding of dysregulated immune function and lipoprotein metabolism with chronic, excessive alcohol consumption.

    Original languageEnglish (US)
    Pages (from-to)899-911
    Number of pages13
    JournalInternational Journal of Neuropsychopharmacology
    Volume14
    Issue number7
    DOIs
    StatePublished - Aug 2011

    Fingerprint

    Self Administration
    Proteomics
    Primates
    Two-Dimensional Difference Gel Electrophoresis
    Biomarkers
    Alcohols
    Clusterin
    Blood Proteins
    Ethanol
    Fibronectins
    Amyloid
    Alcohol Drinking
    Retinol-Binding Proteins
    Serum
    Immunoblotting
    Lipoproteins
    Sensitivity and Specificity
    Proteins

    Keywords

    • Alcohol abuse
    • alcoholism
    • biomarker
    • diagnostic
    • plasma
    • proteomic

    ASJC Scopus subject areas

    • Pharmacology (medical)
    • Pharmacology
    • Psychiatry and Mental health

    Cite this

    Plasma proteomic alterations in non-human primates and humans after chronic alcohol self-administration. / Freeman, Willard M.; Vanguilder, Heather D.; Guidone, Elizabeth; Krystal, John H.; Grant, Kathleen (Kathy); Vrana, Kent E.

    In: International Journal of Neuropsychopharmacology, Vol. 14, No. 7, 08.2011, p. 899-911.

    Research output: Contribution to journalArticle

    Freeman, Willard M. ; Vanguilder, Heather D. ; Guidone, Elizabeth ; Krystal, John H. ; Grant, Kathleen (Kathy) ; Vrana, Kent E. / Plasma proteomic alterations in non-human primates and humans after chronic alcohol self-administration. In: International Journal of Neuropsychopharmacology. 2011 ; Vol. 14, No. 7. pp. 899-911.
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