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Involvement of K(v)1.3 and p38 MAPK signaling in HIV-1 glycoprotein 120-induced microglia neurotoxicity
Inflammatory responses mediated by activated microglia play a pivotal role in the pathogenesis of human immunodeficiency virus type 1 (HIV-1)-associated neurocognitive disorders. Studies on identification of specific targets to control microglia activation and resultant neurotoxic activity are imper...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3270274/ https://www.ncbi.nlm.nih.gov/pubmed/22258405 http://dx.doi.org/10.1038/cddis.2011.140 |
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author | Liu, J Xu, C Chen, L Xu, P Xiong, H |
author_facet | Liu, J Xu, C Chen, L Xu, P Xiong, H |
author_sort | Liu, J |
collection | PubMed |
description | Inflammatory responses mediated by activated microglia play a pivotal role in the pathogenesis of human immunodeficiency virus type 1 (HIV-1)-associated neurocognitive disorders. Studies on identification of specific targets to control microglia activation and resultant neurotoxic activity are imperative. Increasing evidence indicate that voltage-gated K(+) (K(v)) channels are involved in the regulation of microglia functionality. In this study, we investigated K(v)1.3 channels in the regulation of neurotoxic activity mediated by HIV-1 glycoprotein 120 (gp120)-stimulated rat microglia. Our results showed treatment of microglia with gp120 increased the expression levels of K(v)1.3 mRNA and protein. In parallel, whole-cell patch-clamp studies revealed that gp120 enhanced microglia K(v)1.3 current, which was blocked by margatoxin, a K(v)1.3 blocker. The association of gp120 enhancement of K(v)1.3 current with microglia neurotoxicity was demonstrated by experimental results that blocking microglia K(v)1.3 attenuated gp120-associated microglia production of neurotoxins and neurotoxicity. Knockdown of K(v)1.3 gene by transfection of microglia with K(v)1.3-siRNA abrogated gp120-associated microglia neurotoxic activity. Further investigation unraveled an involvement of p38 MAPK in gp120 enhancement of microglia K(v)1.3 expression and resultant neurotoxic activity. These results suggest not only a role K(v)1.3 may have in gp120-associated microglia neurotoxic activity, but also a potential target for the development of therapeutic strategies. |
format | Online Article Text |
id | pubmed-3270274 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-32702742012-02-02 Involvement of K(v)1.3 and p38 MAPK signaling in HIV-1 glycoprotein 120-induced microglia neurotoxicity Liu, J Xu, C Chen, L Xu, P Xiong, H Cell Death Dis Original Article Inflammatory responses mediated by activated microglia play a pivotal role in the pathogenesis of human immunodeficiency virus type 1 (HIV-1)-associated neurocognitive disorders. Studies on identification of specific targets to control microglia activation and resultant neurotoxic activity are imperative. Increasing evidence indicate that voltage-gated K(+) (K(v)) channels are involved in the regulation of microglia functionality. In this study, we investigated K(v)1.3 channels in the regulation of neurotoxic activity mediated by HIV-1 glycoprotein 120 (gp120)-stimulated rat microglia. Our results showed treatment of microglia with gp120 increased the expression levels of K(v)1.3 mRNA and protein. In parallel, whole-cell patch-clamp studies revealed that gp120 enhanced microglia K(v)1.3 current, which was blocked by margatoxin, a K(v)1.3 blocker. The association of gp120 enhancement of K(v)1.3 current with microglia neurotoxicity was demonstrated by experimental results that blocking microglia K(v)1.3 attenuated gp120-associated microglia production of neurotoxins and neurotoxicity. Knockdown of K(v)1.3 gene by transfection of microglia with K(v)1.3-siRNA abrogated gp120-associated microglia neurotoxic activity. Further investigation unraveled an involvement of p38 MAPK in gp120 enhancement of microglia K(v)1.3 expression and resultant neurotoxic activity. These results suggest not only a role K(v)1.3 may have in gp120-associated microglia neurotoxic activity, but also a potential target for the development of therapeutic strategies. Nature Publishing Group 2012-01 2012-01-19 /pmc/articles/PMC3270274/ /pubmed/22258405 http://dx.doi.org/10.1038/cddis.2011.140 Text en Copyright © 2012 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ |
spellingShingle | Original Article Liu, J Xu, C Chen, L Xu, P Xiong, H Involvement of K(v)1.3 and p38 MAPK signaling in HIV-1 glycoprotein 120-induced microglia neurotoxicity |
title | Involvement of K(v)1.3 and p38 MAPK signaling in HIV-1 glycoprotein 120-induced microglia neurotoxicity |
title_full | Involvement of K(v)1.3 and p38 MAPK signaling in HIV-1 glycoprotein 120-induced microglia neurotoxicity |
title_fullStr | Involvement of K(v)1.3 and p38 MAPK signaling in HIV-1 glycoprotein 120-induced microglia neurotoxicity |
title_full_unstemmed | Involvement of K(v)1.3 and p38 MAPK signaling in HIV-1 glycoprotein 120-induced microglia neurotoxicity |
title_short | Involvement of K(v)1.3 and p38 MAPK signaling in HIV-1 glycoprotein 120-induced microglia neurotoxicity |
title_sort | involvement of k(v)1.3 and p38 mapk signaling in hiv-1 glycoprotein 120-induced microglia neurotoxicity |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3270274/ https://www.ncbi.nlm.nih.gov/pubmed/22258405 http://dx.doi.org/10.1038/cddis.2011.140 |
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