Proteomic analyses of monocytes obtained from Hispanic women with HIV-associated dementia show depressed antioxidants
Article first published online: 13 JUL 2010
Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PROTEOMICS - Clinical Applications
Volume 4, Issue 8-9, pages 706–714, September 2010
How to Cite
Kraft-Terry, S., Gerena, Y., Wojna, V., Plaud-Valentin, M., Rodriguez, Y., Ciborowski, P., Mayo, R., Skolasky, R., Gendelman, H. E. and Meléndez, L. M. (2010), Proteomic analyses of monocytes obtained from Hispanic women with HIV-associated dementia show depressed antioxidants. Prot. Clin. Appl., 4: 706–714. doi: 10.1002/prca.201000010
- Issue published online: 13 JUL 2010
- Article first published online: 13 JUL 2010
- Manuscript Accepted: 1 MAY 2010
- Manuscript Revised: 2 APR 2010
- Manuscript Received: 29 JAN 2010
- PR Specialized Neuroscience Program in NeuroAIDS
- NIH-NINDS. Grant Numbers: 1U54NS430, 2 U54 NS43011, R01 MH083516-01, NIH-NCRR-RCMI-CRC-1P20RR11126, NIH-NCRR-RCMI G12 RR-03051
- Clinical Proteomics. Grant Numbers: 5P01 NS31492, 2R37 NS36126, 2R01 NS034239, P20RR15635, U54NS 43011, P01 MH64570, P01 NS43985, 5 POI DA026146-03, 5 P30MH062261-10
- HIV-associated dementia;
- HIV-associated neurocognitive disorders;
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.