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HIV-1 Tat inhibits EAAT-2 through AEG-1 upregulation in models of HIV-associated neurocognitive disorder
During HIV-associated neurocognitive disorder (HAND), decreasing in excitatory amino acid transporter 2 (EAAT-2) in astrocyte plasma membranes leads to elevated levels of extracellular glutamate and, in turn, neuronal apoptosis. We used immunohistochemistry, western blot, qRT-PCR, and RNA interferen...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503662/ https://www.ncbi.nlm.nih.gov/pubmed/28404980 http://dx.doi.org/10.18632/oncotarget.16485 |
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author | Ye, Xiang Zhang, Yu Xu, Qiping Zheng, Honghua Wu, Xiaoyan Qiu, Jinhua Zhang, Zhou Wang, Wei Shao, Yiming Xing, Hui Qin |
author_facet | Ye, Xiang Zhang, Yu Xu, Qiping Zheng, Honghua Wu, Xiaoyan Qiu, Jinhua Zhang, Zhou Wang, Wei Shao, Yiming Xing, Hui Qin |
author_sort | Ye, Xiang |
collection | PubMed |
description | During HIV-associated neurocognitive disorder (HAND), decreasing in excitatory amino acid transporter 2 (EAAT-2) in astrocyte plasma membranes leads to elevated levels of extracellular glutamate and, in turn, neuronal apoptosis. We used immunohistochemistry, western blot, qRT-PCR, and RNA interference to elucidate the molecular mechanisms underlying the decreased EAAT-2 expression during HAND at the tissue and cellular levels. We used simian immunodeficiency virus-human immunodeficiency virus chimeric virus (SHIV)-infected macaques as an in vivo model of HAND. Our results show that EAAT-2 expression was decreased in the cerebral cortex, while AEG-1 expression was increased, and the expression levels of these proteins were negatively correlated. In vitro analyses showed that HIV-1 Tat inhibited EAAT-2 expression by inducing overexpression of AEG-1. More specifically, HIV-1 Tat increased AEG-1 expression via the PI3-K signaling pathway, while increasing EAAT-2 inhibition by YinYan-1 (YY-1) via the NF-κB signaling pathway. These results warrant testing AEG-1 as a potential therapeutic target for treating HAND. |
format | Online Article Text |
id | pubmed-5503662 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-55036622017-07-11 HIV-1 Tat inhibits EAAT-2 through AEG-1 upregulation in models of HIV-associated neurocognitive disorder Ye, Xiang Zhang, Yu Xu, Qiping Zheng, Honghua Wu, Xiaoyan Qiu, Jinhua Zhang, Zhou Wang, Wei Shao, Yiming Xing, Hui Qin Oncotarget Review During HIV-associated neurocognitive disorder (HAND), decreasing in excitatory amino acid transporter 2 (EAAT-2) in astrocyte plasma membranes leads to elevated levels of extracellular glutamate and, in turn, neuronal apoptosis. We used immunohistochemistry, western blot, qRT-PCR, and RNA interference to elucidate the molecular mechanisms underlying the decreased EAAT-2 expression during HAND at the tissue and cellular levels. We used simian immunodeficiency virus-human immunodeficiency virus chimeric virus (SHIV)-infected macaques as an in vivo model of HAND. Our results show that EAAT-2 expression was decreased in the cerebral cortex, while AEG-1 expression was increased, and the expression levels of these proteins were negatively correlated. In vitro analyses showed that HIV-1 Tat inhibited EAAT-2 expression by inducing overexpression of AEG-1. More specifically, HIV-1 Tat increased AEG-1 expression via the PI3-K signaling pathway, while increasing EAAT-2 inhibition by YinYan-1 (YY-1) via the NF-κB signaling pathway. These results warrant testing AEG-1 as a potential therapeutic target for treating HAND. Impact Journals LLC 2017-03-22 /pmc/articles/PMC5503662/ /pubmed/28404980 http://dx.doi.org/10.18632/oncotarget.16485 Text en Copyright: © 2017 Ye et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Review Ye, Xiang Zhang, Yu Xu, Qiping Zheng, Honghua Wu, Xiaoyan Qiu, Jinhua Zhang, Zhou Wang, Wei Shao, Yiming Xing, Hui Qin HIV-1 Tat inhibits EAAT-2 through AEG-1 upregulation in models of HIV-associated neurocognitive disorder |
title | HIV-1 Tat inhibits EAAT-2 through AEG-1 upregulation in models of HIV-associated neurocognitive disorder |
title_full | HIV-1 Tat inhibits EAAT-2 through AEG-1 upregulation in models of HIV-associated neurocognitive disorder |
title_fullStr | HIV-1 Tat inhibits EAAT-2 through AEG-1 upregulation in models of HIV-associated neurocognitive disorder |
title_full_unstemmed | HIV-1 Tat inhibits EAAT-2 through AEG-1 upregulation in models of HIV-associated neurocognitive disorder |
title_short | HIV-1 Tat inhibits EAAT-2 through AEG-1 upregulation in models of HIV-associated neurocognitive disorder |
title_sort | hiv-1 tat inhibits eaat-2 through aeg-1 upregulation in models of hiv-associated neurocognitive disorder |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503662/ https://www.ncbi.nlm.nih.gov/pubmed/28404980 http://dx.doi.org/10.18632/oncotarget.16485 |
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