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Role of FOXO3 Activated by HIV-1 Tat in HIV-Associated Neurocognitive Disorder Neuronal Apoptosis

There are numerous types of pathological changes in human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND), including apoptosis of neurons. HIV-1 transactivator of transcription (Tat) protein, which is encoded by HIV-1, may promote apoptosis in HAND. Forkhead box O3 (FOXO3) is...

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Autores principales: Dong, Huaqian, Ye, Xiang, Zhong, Li, Xu, Jinhong, Qiu, Jinhua, Wang, Jun, Shao, Yiming, Xing, Huiqin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369160/
https://www.ncbi.nlm.nih.gov/pubmed/30778283
http://dx.doi.org/10.3389/fnins.2019.00044
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author Dong, Huaqian
Ye, Xiang
Zhong, Li
Xu, Jinhong
Qiu, Jinhua
Wang, Jun
Shao, Yiming
Xing, Huiqin
author_facet Dong, Huaqian
Ye, Xiang
Zhong, Li
Xu, Jinhong
Qiu, Jinhua
Wang, Jun
Shao, Yiming
Xing, Huiqin
author_sort Dong, Huaqian
collection PubMed
description There are numerous types of pathological changes in human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND), including apoptosis of neurons. HIV-1 transactivator of transcription (Tat) protein, which is encoded by HIV-1, may promote apoptosis in HAND. Forkhead box O3 (FOXO3) is a multispecific transcription factor that has roles in many biological processes, including cellular apoptosis. The aim of this study was to determine whether FOXO3 is activated by HIV-1 Tat and to investigate its role in neuronal apoptosis in HAND. We employed tissue staining and related molecular biological experimental methods to confirm our hypothesis. The in vivo experimental results demonstrated that the expression of nuclear FOXO3 increased in the apoptotic neurons of the cerebral cortexes of rhesus macaques infected with simian human immunodeficiency virus (SHIV). The in vitro investigation showed that HIV-1 Tat activated FOXO3, causing it to move from the cytoplasm to the nucleus via the c-Jun N-terminal kinase (JNK) signaling pathway in SH-SY5Y cells. Moreover, FOXO3 down-regulated expression of the anti-apoptosis gene B-cell lymphoma 2 (Bcl-2) and up-regulated the expression of the pro-apoptosis gene Bcl-2-like 11 (Bim) after entering the nucleus, eventually causing cellular apoptosis. Finally, reduction of nuclear FOXO3 reversed cellular apoptosis. Our results suggest that HIV-1 Tat induces FOXO3 to translocate from the cytoplasm to the nucleus via the JNK signaling pathway, leading to neuronal apoptosis. Agents targeting FOXO3 may provide approaches for restoring neuronal function in HAND.
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spelling pubmed-63691602019-02-18 Role of FOXO3 Activated by HIV-1 Tat in HIV-Associated Neurocognitive Disorder Neuronal Apoptosis Dong, Huaqian Ye, Xiang Zhong, Li Xu, Jinhong Qiu, Jinhua Wang, Jun Shao, Yiming Xing, Huiqin Front Neurosci Neuroscience There are numerous types of pathological changes in human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND), including apoptosis of neurons. HIV-1 transactivator of transcription (Tat) protein, which is encoded by HIV-1, may promote apoptosis in HAND. Forkhead box O3 (FOXO3) is a multispecific transcription factor that has roles in many biological processes, including cellular apoptosis. The aim of this study was to determine whether FOXO3 is activated by HIV-1 Tat and to investigate its role in neuronal apoptosis in HAND. We employed tissue staining and related molecular biological experimental methods to confirm our hypothesis. The in vivo experimental results demonstrated that the expression of nuclear FOXO3 increased in the apoptotic neurons of the cerebral cortexes of rhesus macaques infected with simian human immunodeficiency virus (SHIV). The in vitro investigation showed that HIV-1 Tat activated FOXO3, causing it to move from the cytoplasm to the nucleus via the c-Jun N-terminal kinase (JNK) signaling pathway in SH-SY5Y cells. Moreover, FOXO3 down-regulated expression of the anti-apoptosis gene B-cell lymphoma 2 (Bcl-2) and up-regulated the expression of the pro-apoptosis gene Bcl-2-like 11 (Bim) after entering the nucleus, eventually causing cellular apoptosis. Finally, reduction of nuclear FOXO3 reversed cellular apoptosis. Our results suggest that HIV-1 Tat induces FOXO3 to translocate from the cytoplasm to the nucleus via the JNK signaling pathway, leading to neuronal apoptosis. Agents targeting FOXO3 may provide approaches for restoring neuronal function in HAND. Frontiers Media S.A. 2019-02-04 /pmc/articles/PMC6369160/ /pubmed/30778283 http://dx.doi.org/10.3389/fnins.2019.00044 Text en Copyright © 2019 Dong, Ye, Zhong, Xu, Qiu, Wang, Shao and Xing. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Dong, Huaqian
Ye, Xiang
Zhong, Li
Xu, Jinhong
Qiu, Jinhua
Wang, Jun
Shao, Yiming
Xing, Huiqin
Role of FOXO3 Activated by HIV-1 Tat in HIV-Associated Neurocognitive Disorder Neuronal Apoptosis
title Role of FOXO3 Activated by HIV-1 Tat in HIV-Associated Neurocognitive Disorder Neuronal Apoptosis
title_full Role of FOXO3 Activated by HIV-1 Tat in HIV-Associated Neurocognitive Disorder Neuronal Apoptosis
title_fullStr Role of FOXO3 Activated by HIV-1 Tat in HIV-Associated Neurocognitive Disorder Neuronal Apoptosis
title_full_unstemmed Role of FOXO3 Activated by HIV-1 Tat in HIV-Associated Neurocognitive Disorder Neuronal Apoptosis
title_short Role of FOXO3 Activated by HIV-1 Tat in HIV-Associated Neurocognitive Disorder Neuronal Apoptosis
title_sort role of foxo3 activated by hiv-1 tat in hiv-associated neurocognitive disorder neuronal apoptosis
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369160/
https://www.ncbi.nlm.nih.gov/pubmed/30778283
http://dx.doi.org/10.3389/fnins.2019.00044
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