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.

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.

Paraquat and MPTP alter microRNA expression profiles, and downregulated expression of miR-17-5p contributes to PQ-induced dopaminergic neurodegeneration.

Recent evidence indicates that microRNAs (miRNAs) play a key role in neurodegenerative diseases. However, the toxic effects of paraquat (PQ) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on miRNA expression profiles in dopaminergic neurons have not been investigated. In the present study, we used microarray analysis to show that PQ and MPTP induce alterations of miRNA expression in neuro-2a cells.

Paraquat and MPTP induce neurodegeneration and alteration in the expression profile of microRNAs: the role of transcription factor Nrf2.

Both transcription factors (TFs) and microRNAs (miRNAs) can exert a widespread impact on gene expression. In the present study, we investigated the role of Nrf2 in paraquat-induced intracorporeal neurodegeneration and miRNA expression by exposing Nrf2 wild-type and knockout mice to paraquat (PQ) or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Exposure to 10 mg/kg PQ or 30 mg/kg MPTP caused damage to nerve cells in the substantia nigra (SN) in both Nrf2 (+/+) and Nrf2 (-/-) ICR mice, which included cell morphological changes, detectable apoptosis and a significant reduction in the number of dopaminergic (DA) neurons.

Neuroprotective effects of tert-butylhydroquinone on paraquat-induced dopaminergic cell degeneration in C57BL/6 mice and in PC12 cells.

The present study was aimed at determining the role of paraquat (PQ) in the activation of the NF-E2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway and the possible neuroprotective effects of tert-butylhydroquinone (tBHQ) pretreatment on PQ-induced neurodegeneration in vivo and in vitro. 7 mg/kg PQ treatment of male C57BL/6 mice caused decreased spontaneous locomotor activity, decreased tyrosine hydroxylase (TH)-positive neurons, increased terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end-labeling (TUNEL)-positive cells in the substantia nigra, as well as increased protein levels of both nuclear Nrf2 and HO-1. In PQ-treated mice, pretreatment with 1 % tBHQ (w/w) significantly attenuated impairments in behavioral performance, decreased TH-positive neurons, and increased TUNEL-positive cells in the substantia nigra, as well as increased protein expression of both nuclear Nrf2 and HO-1.

[Antagonism of tert-butylhydroquinone on neurotoxicity and oxidative stress induced by paraquat in PC12].

Objective: To investigate the protective effects of the tert-butylhydroquinone (tBHQ) pretreatment on neurotoxicity and oxidative stress induced by paraquat (PQ) in PC12 cells.

Methods: Cytotoxicity of PC12 cells was measured by MTT assay, following the PC12 cells treatment with different concentrations of 100, 300 micromol/L PQ for 24 h and 48 h. PC12 cells were pretreated with or without 40 micromol/L tBHQ for 4 h, PC12 cells were exposed to PQ at the doses of 0, 100, 300 micromol/L for 24 h and 48 h, respectively.