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

Stephanie Kraft-Terry, Yamil Gerena, Valerie Wojna, Marines Plaud-Valentin, Yolanda Rodriguez, Pawel Ciborowski, Raul Mayo, Richard Skolasky, Howard E. Gendelman, Loyda M. Meléndez

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)706-714
Number of pages9
JournalProteomics - Clinical Applications
Volume4
Issue number8-9
DOIs
StatePublished - Sep 1 2010

Keywords

  • 2-D-DIGE
  • HIV-associated dementia
  • HIV-associated neurocognitive disorders
  • MS
  • Monocytes

ASJC Scopus subject areas

  • Clinical Biochemistry

Fingerprint Dive into the research topics of 'Proteomic analyses of monocytes obtained from Hispanic women with HIV-associated dementia show depressed antioxidants'. Together they form a unique fingerprint.

  • Cite this

    Kraft-Terry, S., Gerena, Y., Wojna, V., Plaud-Valentin, M., Rodriguez, Y., Ciborowski, P., Mayo, R., Skolasky, R., Gendelman, H. E., & Meléndez, L. M. (2010). Proteomic analyses of monocytes obtained from Hispanic women with HIV-associated dementia show depressed antioxidants. Proteomics - Clinical Applications, 4(8-9), 706-714. https://doi.org/10.1002/prca.201000010