Reactive oxygen species regulate miR-17-5p expression via DNA methylation in paraquat-induced nerve cell damage.

Abstract:

:There is emerging evidence suggesting that oxidative stress and DNA methylation can alter miRNA expression. However, little is known on the mechanism of miR-17-5p expression changes in paraquat (PQ)-induced nerve cell damage. In the present study, neuro-2a cells were pretreated with antioxidant N-acetylcysteine (NAC) or DNA methylation inhibitor decitabine (DAC), then exposed to different concentrations of PQ, while the expression levels of miR-17-5p were detected by qRT-PCR. Here, it is showed that PQ downregulated the expression of miR-17-5p dose-dependently in neuro-2a cells. The DNA methylation level was upregulated after PQ exposure, while downregulated with the pretreatment of NAC in the above content, detected by 5-mC immunofluorescence technique. The interaction effect of NAC and PQ in alternating DNA methylation level was further confirmed by flow cytometry. NAC and DAC individually had an interaction effect in PQ-induced nerve cell damage. After using NAC, PQ-induced ROS elevation and DNA methylation are reduced, thereby preventing the proapoptotic effect of miR-17-5p. Above all, PQ can induce DNA methylation variations through ROS production, leading to the downregulation of miR-17-5p expression in PQ-induced nerve cell damage.

journal_name

Environ Toxicol

journal_title

Environmental toxicology

authors

Zhan Y,Guo Z,Zheng F,Zhang Z,Li K,Wang Q,Wang L,Cai Z,Chen N,Wu S,Li H

doi

10.1002/tox.23001

subject

Has Abstract

pub_date

2020-12-01 00:00:00

pages

1364-1373

issue

12

eissn

1520-4081

issn

1522-7278

journal_volume

35

pub_type

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