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Polyamines: Predictive Biomarker for HIV-Associated Neurocognitive Disorders

OBJECTIVES: Spermidine/spermine-N(1)-acetytransferase (SSAT) is the key enzyme in the catabolism of polyamines that are involved in regulating NMDA functioning. Over expression of SSAT leads to abnormal metabolic cycling and may disrupt NMDA receptor signaling. In fact, the HIV protein Tat induces n...

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Autores principales: Merali, Salim, Barrero, Carlos A., Sacktor, Ned C., Haughey, Norman J., Datta, Prasun K., Langford, Dianne, Khalili, Kamel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4397651/
https://www.ncbi.nlm.nih.gov/pubmed/25893137
http://dx.doi.org/10.4172/2155-6113.1000312
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author Merali, Salim
Barrero, Carlos A.
Sacktor, Ned C.
Haughey, Norman J.
Datta, Prasun K.
Langford, Dianne
Khalili, Kamel
author_facet Merali, Salim
Barrero, Carlos A.
Sacktor, Ned C.
Haughey, Norman J.
Datta, Prasun K.
Langford, Dianne
Khalili, Kamel
author_sort Merali, Salim
collection PubMed
description OBJECTIVES: Spermidine/spermine-N(1)-acetytransferase (SSAT) is the key enzyme in the catabolism of polyamines that are involved in regulating NMDA functioning. Over expression of SSAT leads to abnormal metabolic cycling and may disrupt NMDA receptor signaling. In fact, the HIV protein Tat induces neurotoxicity involving polyamine/NMDA receptor interactions. Thus, we investigated abnormal polyamine cycling in HIV+ participants with varying degrees of HIV-associated neurocognitive disorders. METHODS: Acetyl-polyamine (SSAT products) levels were assessed by HPLC in CSF from 99 HIV-infected participants (no cognitive impairment (NCI, n=25), asymptomatic neurocognitive impairment (ANI, n=25), mild cognitive and motor disorders (MCMD, n=24), and HIV-associated dementia (HAD, n=25)). Polyamine levels in brain tissues from a subset of participants (uninfected (n=3), NCI (n=3), and MNCD (n=3)) were also assessed. Human primary astrocytes expressing HIV Tat were assessed for levels of the SSAT activity. RESULTS: Activation of the polyamine catabolic enzyme, SSAT increases polyamine flux in brain and CSF of HIV infected individuals with HIV-associated neurocognitive disorders. CSF levels of acetylated polyamine increase with the degree of HAND severity as indicated by significantly increased acetylpolyamine levels in HAD participants compared to NCI and ANI (p<0.0001) and between MCMD and NCI and ANI (p<0.0001). In vitro studies suggest that the HIV protein Tat may be responsible in part for astrocyte-derived acetyl polyamine release. INTERPRETATION: Our data suggest that polyamine metabolism may play a pivotal role in the neurodegeneration process among HAND patients. Changes in polyamine flux may serve as a potential predictive diagnostic biomarker for different severities of HAND.
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spelling pubmed-43976512015-04-15 Polyamines: Predictive Biomarker for HIV-Associated Neurocognitive Disorders Merali, Salim Barrero, Carlos A. Sacktor, Ned C. Haughey, Norman J. Datta, Prasun K. Langford, Dianne Khalili, Kamel J AIDS Clin Res Article OBJECTIVES: Spermidine/spermine-N(1)-acetytransferase (SSAT) is the key enzyme in the catabolism of polyamines that are involved in regulating NMDA functioning. Over expression of SSAT leads to abnormal metabolic cycling and may disrupt NMDA receptor signaling. In fact, the HIV protein Tat induces neurotoxicity involving polyamine/NMDA receptor interactions. Thus, we investigated abnormal polyamine cycling in HIV+ participants with varying degrees of HIV-associated neurocognitive disorders. METHODS: Acetyl-polyamine (SSAT products) levels were assessed by HPLC in CSF from 99 HIV-infected participants (no cognitive impairment (NCI, n=25), asymptomatic neurocognitive impairment (ANI, n=25), mild cognitive and motor disorders (MCMD, n=24), and HIV-associated dementia (HAD, n=25)). Polyamine levels in brain tissues from a subset of participants (uninfected (n=3), NCI (n=3), and MNCD (n=3)) were also assessed. Human primary astrocytes expressing HIV Tat were assessed for levels of the SSAT activity. RESULTS: Activation of the polyamine catabolic enzyme, SSAT increases polyamine flux in brain and CSF of HIV infected individuals with HIV-associated neurocognitive disorders. CSF levels of acetylated polyamine increase with the degree of HAND severity as indicated by significantly increased acetylpolyamine levels in HAD participants compared to NCI and ANI (p<0.0001) and between MCMD and NCI and ANI (p<0.0001). In vitro studies suggest that the HIV protein Tat may be responsible in part for astrocyte-derived acetyl polyamine release. INTERPRETATION: Our data suggest that polyamine metabolism may play a pivotal role in the neurodegeneration process among HAND patients. Changes in polyamine flux may serve as a potential predictive diagnostic biomarker for different severities of HAND. 2014 /pmc/articles/PMC4397651/ /pubmed/25893137 http://dx.doi.org/10.4172/2155-6113.1000312 Text en Copyright: © 2014 Merali S, et al. http://creativecommons.org/licenses/by/2.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Article
Merali, Salim
Barrero, Carlos A.
Sacktor, Ned C.
Haughey, Norman J.
Datta, Prasun K.
Langford, Dianne
Khalili, Kamel
Polyamines: Predictive Biomarker for HIV-Associated Neurocognitive Disorders
title Polyamines: Predictive Biomarker for HIV-Associated Neurocognitive Disorders
title_full Polyamines: Predictive Biomarker for HIV-Associated Neurocognitive Disorders
title_fullStr Polyamines: Predictive Biomarker for HIV-Associated Neurocognitive Disorders
title_full_unstemmed Polyamines: Predictive Biomarker for HIV-Associated Neurocognitive Disorders
title_short Polyamines: Predictive Biomarker for HIV-Associated Neurocognitive Disorders
title_sort polyamines: predictive biomarker for hiv-associated neurocognitive disorders
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4397651/
https://www.ncbi.nlm.nih.gov/pubmed/25893137
http://dx.doi.org/10.4172/2155-6113.1000312
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