Cargando…

Involvement of Akt/mTOR in the Neurotoxicity of Rotenone-Induced Parkinson’s Disease Models

Rotenone has recently been widely used to establish Parkinson’s disease (PD) models to replicate the features of PD. However, the mechanisms involved in rotenone neurotoxicity have not been elucidated. The aim of the present study was to identify the neurotoxicity of rotenone through intraperitoneal...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Yu, Guo, Hui, Guo, Xinyu, Ge, Denfeng, Shi, Yue, Lu, Xiyu, Lu, Jinli, Chen, Juan, Ding, Fei, Zhang, Qi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6843606/
https://www.ncbi.nlm.nih.gov/pubmed/31658620
http://dx.doi.org/10.3390/ijerph16203811
_version_ 1783468255385485312
author Zhang, Yu
Guo, Hui
Guo, Xinyu
Ge, Denfeng
Shi, Yue
Lu, Xiyu
Lu, Jinli
Chen, Juan
Ding, Fei
Zhang, Qi
author_facet Zhang, Yu
Guo, Hui
Guo, Xinyu
Ge, Denfeng
Shi, Yue
Lu, Xiyu
Lu, Jinli
Chen, Juan
Ding, Fei
Zhang, Qi
author_sort Zhang, Yu
collection PubMed
description Rotenone has recently been widely used to establish Parkinson’s disease (PD) models to replicate the features of PD. However, the mechanisms involved in rotenone neurotoxicity have not been elucidated. The aim of the present study was to identify the neurotoxicity of rotenone through intraperitoneal injection in mice and to investigate the global changes of phosphorylation proteomic profiles in rotenone-injured SH-SY5Y cells through a label-free proteomic analysis using a PTMScan with LC–MS/MS. ICR (Institute of Cancer Research) mice were intraperitoneally injected with different dosages of rotenone (1 mg/kg/d or 3 mg/kg/d) daily for 21 consecutive days. Rotenone caused a dose-dependent decrease in locomotor activities and a decrease in the number of Nissl-positive and tyrosine hydroxylase (TH)-immunoreactive neurons in the substantia nigra pars compacta (SNpc). Here, 194 phosphopeptides on 174 proteins were detected in SH-SY5Y cells, and 37 phosphosites on 33 proteins displayed statistically significant changes in expression after rotenone injury. The downregulation of phosphorylated Akt and mTOR was further confirmed by western blot analysis. A specific Akt activator, SC79, could protect cell viability and induce autophagy in rotenone-injured SH-SY5Y cells. This study indicates the involvement of the Akt/mTOR (mammalian target of rapamycin) signaling pathway in rotenone-injured SH-SY5Y cells and provides molecular information for the neurotoxicity of rotenone.
format Online
Article
Text
id pubmed-6843606
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-68436062019-11-25 Involvement of Akt/mTOR in the Neurotoxicity of Rotenone-Induced Parkinson’s Disease Models Zhang, Yu Guo, Hui Guo, Xinyu Ge, Denfeng Shi, Yue Lu, Xiyu Lu, Jinli Chen, Juan Ding, Fei Zhang, Qi Int J Environ Res Public Health Article Rotenone has recently been widely used to establish Parkinson’s disease (PD) models to replicate the features of PD. However, the mechanisms involved in rotenone neurotoxicity have not been elucidated. The aim of the present study was to identify the neurotoxicity of rotenone through intraperitoneal injection in mice and to investigate the global changes of phosphorylation proteomic profiles in rotenone-injured SH-SY5Y cells through a label-free proteomic analysis using a PTMScan with LC–MS/MS. ICR (Institute of Cancer Research) mice were intraperitoneally injected with different dosages of rotenone (1 mg/kg/d or 3 mg/kg/d) daily for 21 consecutive days. Rotenone caused a dose-dependent decrease in locomotor activities and a decrease in the number of Nissl-positive and tyrosine hydroxylase (TH)-immunoreactive neurons in the substantia nigra pars compacta (SNpc). Here, 194 phosphopeptides on 174 proteins were detected in SH-SY5Y cells, and 37 phosphosites on 33 proteins displayed statistically significant changes in expression after rotenone injury. The downregulation of phosphorylated Akt and mTOR was further confirmed by western blot analysis. A specific Akt activator, SC79, could protect cell viability and induce autophagy in rotenone-injured SH-SY5Y cells. This study indicates the involvement of the Akt/mTOR (mammalian target of rapamycin) signaling pathway in rotenone-injured SH-SY5Y cells and provides molecular information for the neurotoxicity of rotenone. MDPI 2019-10-10 2019-10 /pmc/articles/PMC6843606/ /pubmed/31658620 http://dx.doi.org/10.3390/ijerph16203811 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhang, Yu
Guo, Hui
Guo, Xinyu
Ge, Denfeng
Shi, Yue
Lu, Xiyu
Lu, Jinli
Chen, Juan
Ding, Fei
Zhang, Qi
Involvement of Akt/mTOR in the Neurotoxicity of Rotenone-Induced Parkinson’s Disease Models
title Involvement of Akt/mTOR in the Neurotoxicity of Rotenone-Induced Parkinson’s Disease Models
title_full Involvement of Akt/mTOR in the Neurotoxicity of Rotenone-Induced Parkinson’s Disease Models
title_fullStr Involvement of Akt/mTOR in the Neurotoxicity of Rotenone-Induced Parkinson’s Disease Models
title_full_unstemmed Involvement of Akt/mTOR in the Neurotoxicity of Rotenone-Induced Parkinson’s Disease Models
title_short Involvement of Akt/mTOR in the Neurotoxicity of Rotenone-Induced Parkinson’s Disease Models
title_sort involvement of akt/mtor in the neurotoxicity of rotenone-induced parkinson’s disease models
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6843606/
https://www.ncbi.nlm.nih.gov/pubmed/31658620
http://dx.doi.org/10.3390/ijerph16203811
work_keys_str_mv AT zhangyu involvementofaktmtorintheneurotoxicityofrotenoneinducedparkinsonsdiseasemodels
AT guohui involvementofaktmtorintheneurotoxicityofrotenoneinducedparkinsonsdiseasemodels
AT guoxinyu involvementofaktmtorintheneurotoxicityofrotenoneinducedparkinsonsdiseasemodels
AT gedenfeng involvementofaktmtorintheneurotoxicityofrotenoneinducedparkinsonsdiseasemodels
AT shiyue involvementofaktmtorintheneurotoxicityofrotenoneinducedparkinsonsdiseasemodels
AT luxiyu involvementofaktmtorintheneurotoxicityofrotenoneinducedparkinsonsdiseasemodels
AT lujinli involvementofaktmtorintheneurotoxicityofrotenoneinducedparkinsonsdiseasemodels
AT chenjuan involvementofaktmtorintheneurotoxicityofrotenoneinducedparkinsonsdiseasemodels
AT dingfei involvementofaktmtorintheneurotoxicityofrotenoneinducedparkinsonsdiseasemodels
AT zhangqi involvementofaktmtorintheneurotoxicityofrotenoneinducedparkinsonsdiseasemodels