Implications of alpha-synuclein nitration at tyrosine 39 in methamphetamine-induced neurotoxicity in vitro and in vivo
Methamphetamine is an amphetamine-type psychostimulant that can damage dopaminergic neurons and cause characteristic pathological changes similar to neurodegenerative diseases such as Parkinson’s disease. However, its specific mechanism of action is still unclear. In the present study, we establishe...
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doaj-6930636bcdcb4969951d92a500211f4f2020-11-25T03:40:15ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53742019-01-0114231932710.4103/1673-5374.244795Implications of alpha-synuclein nitration at tyrosine 39 in methamphetamine-induced neurotoxicity in vitro and in vivoHong-Hua QiaoLin-Nan ZhuYue WangJia-Liang HuiWei-Bing XieChao LiuLing ChenPing-Ming QiuMethamphetamine is an amphetamine-type psychostimulant that can damage dopaminergic neurons and cause characteristic pathological changes similar to neurodegenerative diseases such as Parkinson’s disease. However, its specific mechanism of action is still unclear. In the present study, we established a Parkinson’s disease pathology model by exposing SH-SY5Y cells and C57BL/6J mice to methamphetamine. In vitro experiments were performed with 0, 0.5, 1.0, 1.5, 2.0 or 2.5 mM methamphetamine for 24 hours or 2.0 mM methamphetamine for 0-, 2-, 4-, 8-, 16-, and 24-hour culture of SH-SY5Y cells. Additional experimental groups of SH-SY5Y cells were administered a nitric oxide inhibitor, 0.1 mM N-nitro-L-arginine, 1 hour before exposure to 2.0 mM methamphetamine for 24 hours. In vivo experiments: C57BL/6J mice were intraperitoneally injected with N-nitro-L-arginine (8 mg/kg), eight times, at intervals of 12 hours. Methamphetamine 15 mg/kg was intraperitoneally injected eight times, at intervals of 12 hours, but 0.5-hour after each N-nitro-L-arginine injection in the combined group. Western blot assay was used to determine the expression of nitric oxide synthase, α-synuclein (α-Syn), 5G4, nitrated α-synuclein at the residue Tyr39 (nT39 α-Syn), cleaved caspase-3, and cleaved poly ADP-ribose polymerase (PARP) in cells and mouse brain tissue. Immunofluorescence staining was conducted to measure the positive reaction of NeuN, nT39 α-Syn and 5G4. Enzyme linked immunosorbent assay was performed to determine the dopamine levels in the mouse brain. After methamphetamine exposure, α-Syn expression increased; the aggregation of α-Syn 5G4 increased; nT39 α-Syn, nitric oxide synthase, cleaved caspase-3, and cleaved PARP expression increased in the cultures of SH-SY5Y cells and in the brains of C57BL/6J mice; and dopamine levels were reduced in the mouse brain. These changes were markedly reduced when N-nitro-L-arginine was administered with methamphetamine in both SH-SY5Y cells and C57BL/6J mice. These results suggest that nT39 α-Syn aggregation is involved in methamphetamine neurotoxicity.http://www.nrronline.org/article.asp?issn=1673-5374;year=2019;volume=14;issue=2;spage=319;epage=327;aulast=Qiaonerve regeneration; alpha-synuclein; nitrated α-synuclein; Parkinson′s disease; methamphetamine; N-nitro-L-arginine; alpha-synuclein aggregation; apoptosis; neurotoxicity; neural regeneration |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hong-Hua Qiao Lin-Nan Zhu Yue Wang Jia-Liang Hui Wei-Bing Xie Chao Liu Ling Chen Ping-Ming Qiu |
spellingShingle |
Hong-Hua Qiao Lin-Nan Zhu Yue Wang Jia-Liang Hui Wei-Bing Xie Chao Liu Ling Chen Ping-Ming Qiu Implications of alpha-synuclein nitration at tyrosine 39 in methamphetamine-induced neurotoxicity in vitro and in vivo Neural Regeneration Research nerve regeneration; alpha-synuclein; nitrated α-synuclein; Parkinson′s disease; methamphetamine; N-nitro-L-arginine; alpha-synuclein aggregation; apoptosis; neurotoxicity; neural regeneration |
author_facet |
Hong-Hua Qiao Lin-Nan Zhu Yue Wang Jia-Liang Hui Wei-Bing Xie Chao Liu Ling Chen Ping-Ming Qiu |
author_sort |
Hong-Hua Qiao |
title |
Implications of alpha-synuclein nitration at tyrosine 39 in methamphetamine-induced neurotoxicity in vitro and in vivo |
title_short |
Implications of alpha-synuclein nitration at tyrosine 39 in methamphetamine-induced neurotoxicity in vitro and in vivo |
title_full |
Implications of alpha-synuclein nitration at tyrosine 39 in methamphetamine-induced neurotoxicity in vitro and in vivo |
title_fullStr |
Implications of alpha-synuclein nitration at tyrosine 39 in methamphetamine-induced neurotoxicity in vitro and in vivo |
title_full_unstemmed |
Implications of alpha-synuclein nitration at tyrosine 39 in methamphetamine-induced neurotoxicity in vitro and in vivo |
title_sort |
implications of alpha-synuclein nitration at tyrosine 39 in methamphetamine-induced neurotoxicity in vitro and in vivo |
publisher |
Wolters Kluwer Medknow Publications |
series |
Neural Regeneration Research |
issn |
1673-5374 |
publishDate |
2019-01-01 |
description |
Methamphetamine is an amphetamine-type psychostimulant that can damage dopaminergic neurons and cause characteristic pathological changes similar to neurodegenerative diseases such as Parkinson’s disease. However, its specific mechanism of action is still unclear. In the present study, we established a Parkinson’s disease pathology model by exposing SH-SY5Y cells and C57BL/6J mice to methamphetamine. In vitro experiments were performed with 0, 0.5, 1.0, 1.5, 2.0 or 2.5 mM methamphetamine for 24 hours or 2.0 mM methamphetamine for 0-, 2-, 4-, 8-, 16-, and 24-hour culture of SH-SY5Y cells. Additional experimental groups of SH-SY5Y cells were administered a nitric oxide inhibitor, 0.1 mM N-nitro-L-arginine, 1 hour before exposure to 2.0 mM methamphetamine for 24 hours. In vivo experiments: C57BL/6J mice were intraperitoneally injected with N-nitro-L-arginine (8 mg/kg), eight times, at intervals of 12 hours. Methamphetamine 15 mg/kg was intraperitoneally injected eight times, at intervals of 12 hours, but 0.5-hour after each N-nitro-L-arginine injection in the combined group. Western blot assay was used to determine the expression of nitric oxide synthase, α-synuclein (α-Syn), 5G4, nitrated α-synuclein at the residue Tyr39 (nT39 α-Syn), cleaved caspase-3, and cleaved poly ADP-ribose polymerase (PARP) in cells and mouse brain tissue. Immunofluorescence staining was conducted to measure the positive reaction of NeuN, nT39 α-Syn and 5G4. Enzyme linked immunosorbent assay was performed to determine the dopamine levels in the mouse brain. After methamphetamine exposure, α-Syn expression increased; the aggregation of α-Syn 5G4 increased; nT39 α-Syn, nitric oxide synthase, cleaved caspase-3, and cleaved PARP expression increased in the cultures of SH-SY5Y cells and in the brains of C57BL/6J mice; and dopamine levels were reduced in the mouse brain. These changes were markedly reduced when N-nitro-L-arginine was administered with methamphetamine in both SH-SY5Y cells and C57BL/6J mice. These results suggest that nT39 α-Syn aggregation is involved in methamphetamine neurotoxicity. |
topic |
nerve regeneration; alpha-synuclein; nitrated α-synuclein; Parkinson′s disease; methamphetamine; N-nitro-L-arginine; alpha-synuclein aggregation; apoptosis; neurotoxicity; neural regeneration |
url |
http://www.nrronline.org/article.asp?issn=1673-5374;year=2019;volume=14;issue=2;spage=319;epage=327;aulast=Qiao |
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