Proteomic analyses of monocytes obtained from Hispanic women with HIV-associated dementia show depressed antioxidants

Authors

  • Stephanie Kraft-Terry,

    1. Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA
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  • Yamil Gerena,

    1. Specialized Neuroscience Program in NeuroAIDS, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
    2. Department of Pharmaceutical Sciences, School of Pharmacy, and Department of Pharmacology, School of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
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  • Valerie Wojna,

    1. Specialized Neuroscience Program in NeuroAIDS, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
    2. Internal Medicine, Neurology Division, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
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  • Marines Plaud-Valentin,

    1. Specialized Neuroscience Program in NeuroAIDS, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
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  • Yolanda Rodriguez,

    1. Specialized Neuroscience Program in NeuroAIDS, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
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  • Pawel Ciborowski,

    1. Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA
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  • Raul Mayo,

    1. Specialized Neuroscience Program in NeuroAIDS, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
    2. Physical Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
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  • Richard Skolasky,

    1. Department of Orthopedic Surgery, Johns Hopkins University, Baltimore, MD, USA
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  • Howard E. Gendelman,

    1. Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA
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  • Loyda M. Meléndez

    Corresponding author
    1. Specialized Neuroscience Program in NeuroAIDS, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
    2. Department of Microbiology, School of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
    • Department of Microbiology, School of Medicine, Medical Sciences Campus, San Juan 00935, Puerto Rico Fax: +1-787-777-0078
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Abstract

Purpose: Monocyte ingress into the brain during progressive human immunodeficiency virus (HIV-1) infection parallels the severity of cognitive impairments. Although activated monocyte phenotypes emerge in disease, the functional correlates of these cells remain unresolved.

Experimental design: To this end, we studied the proteome of blood-derived monocytes obtained from Hispanic women with the most severe form of HIV-associated neurocognitive disorders, HIV-associated dementia (HAD). Monocytes isolated from peripheral blood mononuclear cells by CD14+ immunoaffinity column chromatography were >95% pure. Cells were recovered from four patients without evidence of cognitive impairment and five with HAD and analyzed by 2-D DIGE and tandem MS.

Results: Importantly, ADP ribosylhydrolase, myeloperoxidase, thioredoxin, peroxiredoxin 3, NADPH, and GTPase-activating protein were all downregulated in HAD. In regards to myeloperoxidase, thioredoxin, and peroxiredoxin 3, these changes were validated in an additional cohort of 30 patients by flow cytometry.

Conclusions and clinical relevance: We conclude that deficits in monocyte antioxidants lead to neuronal damage through the loss of hydrogen peroxide scavenging capabilities; thus exposing neurons to apoptosis-inducing factors. Altered monocyte functions therefore may contribute to the development and progression of cognitive impairment.

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