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


METHODS
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
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.
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.
Stephanie
S
Kraft-Terry
Yamil
Y
Gerena
Valerie
V
Wojna
Marines
M
Plaud-Valentin
Yolanda
Y
Rodriguez
Pawel
P
Ciborowski
Raul
R
Mayo
Richard
R
Skolasky
Howard E
HE
Gendelman
Loyda M
LM
Meléndez
D015526:AIDS Dementia Complex / Q000097:blood / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D000328:Adult; D000975:Antioxidants / Q000378:metabolism*; D002846:Chromatography, Affinity; D005260:Female; D016166:Free Radical Scavengers / Q000378:metabolism; D006630:Hispanic or Latino; D006801:Humans; D007158:Immunologic Techniques; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism* / Q000821:virology; D009195:Peroxidase / Q000378:metabolism; D054464:Peroxiredoxins / Q000378:metabolism; D020543:Proteome / Q000032:analysis*; D013879:Thioredoxins / Q000378:metabolism
D000975:Antioxidants; D016166:Free Radical Scavengers; D020543:Proteome; D013879:Thioredoxins; D054464:Peroxiredoxins; D009195:Peroxidase