Document Detail


Cathepsin B and cystatin B in HIV-seropositive women are associated with infection and HIV-1-associated neurocognitive disorders.
MedLine Citation:
PMID:  23291538     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: HIV-1-associated neurocognitive disorders (HAND) is triggered by immune activation of brain cells and remain prevalent during progressive viral infection despite antiretroviral therapy. Cathepsins and cystatins are lysosomal proteins secreted by macrophages and microglia, and may play important roles in neuroregulatory responses. Our laboratory has shown increased secretion and neurotoxicity of cathepsin B from in-vitro HIV-infected monocyte-derived macrophages, and increased expression in postmortem brain tissue with HIV encephalitis and HAND. We hypothesized that cystatin B and cathepsin B could represent potential biomarkers for HAND.
METHODS: Monocytes, plasma, and cerebrospinal fluid (CSF) from retrospective samples from 63 HIV-seropositive Hispanic women were selected for this study. These were stratified as 27 normal, 14 asymptomatic, and 22 HIV dementia, and as 14 progressors and 17 nonprogressors. Samples were evaluated for cystatins B and C and cathepsin B expression and activity.
RESULTS: Increased cathepsin B and cystatins B and C were found in plasma of HIV-seropositive women. Higher intracellular expression of cathepsin B and cystatin B were found in monocytes from women with HIV-associated dementia (P < 0.05). Significant increase in cystatin B concentration in CSF was found in women with dementia compared with HIV-seropositive asymptomatic women.
CONCLUSION: These results demonstrate that dysregulation of cystatin B-cathepsin B system is operative in HIV-associated neurocognitive impairment and suggests that intracellular expression of cystatin B and cathepsin B in monocytes could be potential candidate biomarkers for HIV dementia, whereas increased cathepsin B and cystatins B and C in plasma are potential candidate markers of chronic HIV-1 activation.
Authors:
Yisel Cantres-Rosario; Marines Plaud-Valentín; Yamil Gerena; Richard L Skolasky; Valerie Wojna; Loyda M Meléndez
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  AIDS (London, England)     Volume:  27     ISSN:  1473-5571     ISO Abbreviation:  AIDS     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-07     Completed Date:  2013-06-10     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  8710219     Medline TA:  AIDS     Country:  England    
Other Details:
Languages:  eng     Pagination:  347-56     Citation Subset:  IM; X    
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MeSH Terms
Descriptor/Qualifier:
AIDS Dementia Complex / epidemiology,  metabolism*,  physiopathology
Adult
Biological Markers / metabolism
Blood-Brain Barrier / metabolism
Cathepsin B* / metabolism
Cystatin B* / metabolism
Disease Progression
Female
Flow Cytometry
HIV Seropositivity / epidemiology,  metabolism*,  physiopathology
HIV-1 / metabolism*
Hispanic Americans / statistics & numerical data*
Humans
Longitudinal Studies
Monocytes / metabolism
Neuropsychological Tests
United States / epidemiology
Up-Regulation
Viral Load
Grant Support
ID/Acronym/Agency:
2G12-RR003051/RR/NCRR NIH HHS; 8G12-MD007600/MD/NIMHD NIH HHS; G12 RR003051/RR/NCRR NIH HHS; P20 RR011126/RR/NCRR NIH HHS; R01 MH083516/MH/NIMH NIH HHS; R01MH083516/MH/NIMH NIH HHS; R25 GM061838/GM/NIGMS NIH HHS; R25 MH080661/MH/NIMH NIH HHS; R25GM061838/GM/NIGMS NIH HHS; U54 NS043011/NS/NINDS NIH HHS; U54NS043011/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Biological Markers; 88844-95-5/Cystatin B; EC 3.4.22.1/Cathepsin B
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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