TY - JOUR
T1 - Proteomic analyses of monocytes obtained from Hispanic women with HIV-associated dementia show depressed antioxidants
AU - Kraft-Terry, Stephanie
AU - Gerena, Yamil
AU - Wojna, Valerie
AU - Plaud-Valentin, Marines
AU - Rodriguez, Yolanda
AU - Ciborowski, Pawel
AU - Mayo, Raul
AU - Skolasky, Richard
AU - Gendelman, Howard E.
AU - Meléndez, Loyda M.
PY - 2010/9
Y1 - 2010/9
N2 - 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.
AB - 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.
KW - 2-D-DIGE
KW - HIV-associated dementia
KW - HIV-associated neurocognitive disorders
KW - MS
KW - Monocytes
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U2 - 10.1002/prca.201000010
DO - 10.1002/prca.201000010
M3 - Article
C2 - 21137088
AN - SCOPUS:78650462323
SN - 1862-8346
VL - 4
SP - 706
EP - 714
JO - Proteomics - Clinical Applications
JF - Proteomics - Clinical Applications
IS - 8-9
ER -