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Toxicol Lett. 2018 Jul;291:11-28. doi: 10.1016/j.toxlet.2018.04.002. Epub 2018 Apr 5.

Paraquat and MPTP induce alteration in the expression profile of long noncoding RNAs in the substantia nigra of mice: Role of the transcription factor Nrf2.

Author information

1
Department of Preventive Medicine, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Department of Endemic Disease Prevention and Control, Fujian Center For Disease Control & Prevention, Fuzhou 350122, China.
2
Department of Preventive Medicine, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou 350122, China.
3
Department of Preventive Medicine, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Department of Environmental and Occupational Health Sciences, University of Louisville, 485 E. Gray Street, Louisville, KY 40202, USA.
4
Department of Epidemiology and Health Statistics, The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350122, China. Electronic address: fmuwsy@163.com.
5
Department of Preventive Medicine, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou 350122, China. Electronic address: fmulhy@163.com.

Abstract

Parkinson's disease (PD) is a common age-related degenerative disease of the central nervous system caused mainly by hereditary, pesticides, metals, and polychlorinated biphenyls. Paraquat (PQ), a widely used herbicide, causes PD. Long noncoding RNAs (lncRNAs) are nonprotein-coding transcripts, expressed in the brain and play irreplaceable roles in neurodegenerative diseases. NF-E2-related factor-2 (Nrf2) is an important genetic transcription regulator in oxidative stress. We aimed to discover novel PQ or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-Nrf2-related lncRNAs and explore their association with PD. 17157 lncRNAs and 13707 mRNAs (fold change ≥2, P < 0.05) were identified by Microarray. And the expressions of six lncRNAs were confirmed by using qRT-PCR and two by FISH. Coding-noncoding analysis and qRT-PCR were applied to discover the functions of lncRNAs and predict the targeted genes. In mice, PQ and MPTP exposure caused alteration of the lncRNA expression profile, suggesting lncRNAs may be involved in PQ- and MPTP-induced neurotoxicity. The changes in their lncRNA expression were distinct but related. PQ caused lncRNA expression profiling alteration in the substantia nigra (SN) through an interaction with Nrf2, thus changing the NR_027648/Zc3h14/Cybb and NR_030777/Zfp326/Cpne5 mRNA pathways. Similarly, MPTP caused lncRNA expression profiling alteration in SN through an interaction with Nrf2. Nrf2 may be involved in the development of neurodegeneration induced by PQ and MPTP via interaction with lncRNAs as the molecular mechanism. Our findings indicate the potential roles of lncRNAs in the development of PD by PQ or MPTP and provide positive insights into future mechanism studies.

KEYWORDS:

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; LncRNA; Neurodegeneration; Nrf2; Paraquat; Toxicoepigenetics

PMID:
29627306
DOI:
10.1016/j.toxlet.2018.04.002
[Indexed for MEDLINE]

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