Proteomic analyses of monocytes obtained from Hispanic women with HIV‐associated dementia show depressed antioxidants
- 13 July 2010
- journal article
- research article
- Published by Wiley in Proteomics – Clinical Applications
- Vol. 4 (8-9), 706-714
- https://doi.org/10.1002/prca.201000010
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.Keywords
Funding Information
- PR Specialized Neuroscience Program in NeuroAIDS
- NIH-NINDS (1U54NS430, 2 U54 NS43011, R01 MH083516-01, NIH-NCRR-RCMI-CRC-1P20RR11126, NIH-NCRR-RCMI G12 RR-03051)
- Clinical Proteomics (5P01 NS31492, 2R37 NS36126, 2R01 NS034239, P20RR15635, U54NS 43011, P01 MH64570, P01 NS43985, 5 POI DA026146-03, 5 P30MH062261-10)
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