Cathepsin B and cystatin B in HIV-seropositive women are associated with infection and HIV-1-associated neurocognitive disorders.
Enviado por Loyda Milagros Melendez, Ph.D. el
Título | Cathepsin B and cystatin B in HIV-seropositive women are associated with infection and HIV-1-associated neurocognitive disorders. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Autores | Cantres-Rosario, Y, Plaud-Valentin, M, Gerena, Y, Skolasky, RL, Wojna, V, Melendez, LM |
Journal | AIDS |
Volume | 27 |
Issue | 3 |
Pagination | 347-56 |
Date Published | 2013 Jan 28 |
ISSN | 1473-5571 |
Palabras clave | Adult, AIDS Dementia Complex, Biological Markers, Blood-Brain Barrier, Cathepsin B, Cystatin B, Disease Progression, Female, Flow Cytometry, Hispanic Americans, HIV Seropositivity, HIV-1, Humans, Longitudinal Studies, Monocytes, Neuropsychological Tests, United States, Up-Regulation, Viral Load |
Abstract | 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. |
DOI | 10.1097/QAD.0b013e32835b3e47 |
Alternate Journal | AIDS |
PubMed ID | 23291538 |
PubMed Central ID | PMC3593054 |
Grant List | 2G12-RR003051 / RR / NCRR NIH HHS / United States 8G12-MD007600 / MD / NIMHD NIH HHS / United States G12 RR003051 / RR / NCRR NIH HHS / United States P20 RR011126 / RR / NCRR NIH HHS / United States R01 MH083516 / MH / NIMH NIH HHS / United States R01MH083516 / MH / NIMH NIH HHS / United States R25 GM061838 / GM / NIGMS NIH HHS / United States R25 MH080661 / MH / NIMH NIH HHS / United States R25GM061838 / GM / NIGMS NIH HHS / United States U54 NS043011 / NS / NINDS NIH HHS / United States U54NS043011 / NS / NINDS NIH HHS / United States |