Autophagy Induction by HIV-Tat and Methamphetamine in Primary Midbrain Neuronal Cells of Tree Shrews via the mTOR Signaling and ATG5/ATG7 Pathway
Background: Addictive stimulant drugs, such as methamphetamine (METH), increase the risk of exposure to the human immunodeficiency virus-1 (HIV-1) infection and thus predispose individuals to the development of HIV-associated neurocognitive disorders (HANDs). Previous studies have indicated that HIV...
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Frontiers Media S.A.
2018-12-01
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Series: | Frontiers in Neuroscience |
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Online Access: | https://www.frontiersin.org/article/10.3389/fnins.2018.00921/full |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Juan Li Juan Li Wenguang Wang Pinfen Tong Chi-Kwan Leung Chi-Kwan Leung Genmeng Yang Zhen Li Na Li Xiaomei Sun Yuanyuan Han Caixia Lu Dexuan Kuang Jiejie Dai Xiaofeng Zeng |
spellingShingle |
Juan Li Juan Li Wenguang Wang Pinfen Tong Chi-Kwan Leung Chi-Kwan Leung Genmeng Yang Zhen Li Na Li Xiaomei Sun Yuanyuan Han Caixia Lu Dexuan Kuang Jiejie Dai Xiaofeng Zeng Autophagy Induction by HIV-Tat and Methamphetamine in Primary Midbrain Neuronal Cells of Tree Shrews via the mTOR Signaling and ATG5/ATG7 Pathway Frontiers in Neuroscience HIV-Tat METH autophagy dopaminergic neuronal cells tree shrew |
author_facet |
Juan Li Juan Li Wenguang Wang Pinfen Tong Chi-Kwan Leung Chi-Kwan Leung Genmeng Yang Zhen Li Na Li Xiaomei Sun Yuanyuan Han Caixia Lu Dexuan Kuang Jiejie Dai Xiaofeng Zeng |
author_sort |
Juan Li |
title |
Autophagy Induction by HIV-Tat and Methamphetamine in Primary Midbrain Neuronal Cells of Tree Shrews via the mTOR Signaling and ATG5/ATG7 Pathway |
title_short |
Autophagy Induction by HIV-Tat and Methamphetamine in Primary Midbrain Neuronal Cells of Tree Shrews via the mTOR Signaling and ATG5/ATG7 Pathway |
title_full |
Autophagy Induction by HIV-Tat and Methamphetamine in Primary Midbrain Neuronal Cells of Tree Shrews via the mTOR Signaling and ATG5/ATG7 Pathway |
title_fullStr |
Autophagy Induction by HIV-Tat and Methamphetamine in Primary Midbrain Neuronal Cells of Tree Shrews via the mTOR Signaling and ATG5/ATG7 Pathway |
title_full_unstemmed |
Autophagy Induction by HIV-Tat and Methamphetamine in Primary Midbrain Neuronal Cells of Tree Shrews via the mTOR Signaling and ATG5/ATG7 Pathway |
title_sort |
autophagy induction by hiv-tat and methamphetamine in primary midbrain neuronal cells of tree shrews via the mtor signaling and atg5/atg7 pathway |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Neuroscience |
issn |
1662-453X |
publishDate |
2018-12-01 |
description |
Background: Addictive stimulant drugs, such as methamphetamine (METH), increase the risk of exposure to the human immunodeficiency virus-1 (HIV-1) infection and thus predispose individuals to the development of HIV-associated neurocognitive disorders (HANDs). Previous studies have indicated that HIV-Tat (the transactivator of transcription) and METH can synergistically induce autophagy in SH-SY5Y neuroblastoma cells and that autophagy plays a pivotal role in the neuronal dysfunction in HANDs. However, the underlying mechanism of METH-and HIV-Tat-induced neuronal autophagy remains unclear.Methods: We cultured primary midbrain neuronal cells of tree shrews and treated them with METH and HIV-Tat to study the role of METH and HIV-Tat in inducing autophagy. We evaluated the effects of the single or combined treatment of METH and HIV-Tat on the protein expressions of the autophagy-related genes, including Beclin-1 and LC3B, ATG5, and ATG7 in METH and HIV-Tat-induced autophagy. In addition, the presence of autophagosomes in the METH and/or HIV-Tat treatment was revealed using transmission electron microscopy.Results: The results indicated that METH increased the protein levels of LC3B and Beclin-1, and these effects were significantly enhanced by HIV-Tat. Moreover, the results suggested that ATG5 and ATG7 were involved in the METH and HIV-Tat-induced autophagy. In addition, it was found that mTOR inhibition via pharmacological intervention could trigger autophagy and promote METH and HIV-Tat-induced autophagy.Discussion: Overall, this study contributes to the knowledge of the molecular underpinnings of METH and HIV-Tat-induced autophagy in primary midbrain neuronal cells. Our findings may facilitate the development of therapeutic strategies for METH-and HIV-Tat-induced autophagy in HANDs. |
topic |
HIV-Tat METH autophagy dopaminergic neuronal cells tree shrew |
url |
https://www.frontiersin.org/article/10.3389/fnins.2018.00921/full |
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doaj-a19ca1c5f34148ada646457a0d8d6da82020-11-25T00:35:18ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2018-12-011210.3389/fnins.2018.00921420279Autophagy Induction by HIV-Tat and Methamphetamine in Primary Midbrain Neuronal Cells of Tree Shrews via the mTOR Signaling and ATG5/ATG7 PathwayJuan Li0Juan Li1Wenguang Wang2Pinfen Tong3Chi-Kwan Leung4Chi-Kwan Leung5Genmeng Yang6Zhen Li7Na Li8Xiaomei Sun9Yuanyuan Han10Caixia Lu11Dexuan Kuang12Jiejie Dai13Xiaofeng Zeng14Center of Tree Shrew Germplasm Resources, Institute of Medical Biology, The Chinese Academy of Medical Science and Peking Union Medical College, Kunming, ChinaSchool of Basic Medicine, Kunming Medical University, Kunming, ChinaCenter of Tree Shrew Germplasm Resources, Institute of Medical Biology, The Chinese Academy of Medical Science and Peking Union Medical College, Kunming, ChinaCenter of Tree Shrew Germplasm Resources, Institute of Medical Biology, The Chinese Academy of Medical Science and Peking Union Medical College, Kunming, ChinaSchool of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, ChinaChinese University of Hong Kong – Shandong University (CUHK-SDU) Joint Laboratory of Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, ChinaSchool of Forensic Medicine, Kunming Medical University, Kunming, ChinaSchool of Forensic Medicine, Kunming Medical University, Kunming, ChinaCenter of Tree Shrew Germplasm Resources, Institute of Medical Biology, The Chinese Academy of Medical Science and Peking Union Medical College, Kunming, ChinaCenter of Tree Shrew Germplasm Resources, Institute of Medical Biology, The Chinese Academy of Medical Science and Peking Union Medical College, Kunming, ChinaCenter of Tree Shrew Germplasm Resources, Institute of Medical Biology, The Chinese Academy of Medical Science and Peking Union Medical College, Kunming, ChinaCenter of Tree Shrew Germplasm Resources, Institute of Medical Biology, The Chinese Academy of Medical Science and Peking Union Medical College, Kunming, ChinaCenter of Tree Shrew Germplasm Resources, Institute of Medical Biology, The Chinese Academy of Medical Science and Peking Union Medical College, Kunming, ChinaCenter of Tree Shrew Germplasm Resources, Institute of Medical Biology, The Chinese Academy of Medical Science and Peking Union Medical College, Kunming, ChinaSchool of Forensic Medicine, Kunming Medical University, Kunming, ChinaBackground: Addictive stimulant drugs, such as methamphetamine (METH), increase the risk of exposure to the human immunodeficiency virus-1 (HIV-1) infection and thus predispose individuals to the development of HIV-associated neurocognitive disorders (HANDs). Previous studies have indicated that HIV-Tat (the transactivator of transcription) and METH can synergistically induce autophagy in SH-SY5Y neuroblastoma cells and that autophagy plays a pivotal role in the neuronal dysfunction in HANDs. However, the underlying mechanism of METH-and HIV-Tat-induced neuronal autophagy remains unclear.Methods: We cultured primary midbrain neuronal cells of tree shrews and treated them with METH and HIV-Tat to study the role of METH and HIV-Tat in inducing autophagy. We evaluated the effects of the single or combined treatment of METH and HIV-Tat on the protein expressions of the autophagy-related genes, including Beclin-1 and LC3B, ATG5, and ATG7 in METH and HIV-Tat-induced autophagy. In addition, the presence of autophagosomes in the METH and/or HIV-Tat treatment was revealed using transmission electron microscopy.Results: The results indicated that METH increased the protein levels of LC3B and Beclin-1, and these effects were significantly enhanced by HIV-Tat. Moreover, the results suggested that ATG5 and ATG7 were involved in the METH and HIV-Tat-induced autophagy. In addition, it was found that mTOR inhibition via pharmacological intervention could trigger autophagy and promote METH and HIV-Tat-induced autophagy.Discussion: Overall, this study contributes to the knowledge of the molecular underpinnings of METH and HIV-Tat-induced autophagy in primary midbrain neuronal cells. Our findings may facilitate the development of therapeutic strategies for METH-and HIV-Tat-induced autophagy in HANDs.https://www.frontiersin.org/article/10.3389/fnins.2018.00921/fullHIV-TatMETHautophagydopaminergic neuronal cellstree shrew |