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

Yu Zhang, Hui Guo, Xinyu Guo, Denfeng Ge, Yue Shi, Xiyu Lu, Jinli Lu, Juan Chen, Fei Ding and Qi Zhang
Additional contact information
Yu Zhang: School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, China
Hui Guo: Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong 226001, China
Xinyu Guo: School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, China
Denfeng Ge: School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, China
Yue Shi: School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, China
Xiyu Lu: School of Medicine, Nantong University, 19 Qixiu Road, Nantong 226001, China
Jinli Lu: Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong 226001, China
Juan Chen: Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong 226001, China
Fei Ding: Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong 226001, China
Qi Zhang: Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong 226001, China

IJERPH, 2019, vol. 16, issue 20, 1-15

Abstract: 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.

Keywords: rotenone; Parkinson’s disease; neurotoxicity; Akt; mTOR (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2019
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.mdpi.com/1660-4601/16/20/3811/pdf (application/pdf)
https://www.mdpi.com/1660-4601/16/20/3811/ (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:gam:jijerp:v:16:y:2019:i:20:p:3811-:d:274754

Access Statistics for this article

IJERPH is currently edited by Ms. Jenna Liu

More articles in IJERPH from MDPI
Bibliographic data for series maintained by MDPI Indexing Manager ().