4.7 Article

Reactive oxygen species regulatemiR-17-5p expression viaDNAmethylation in paraquat-induced nerve cell damage

期刊

ENVIRONMENTAL TOXICOLOGY
卷 35, 期 12, 页码 1364-1373

出版社

WILEY
DOI: 10.1002/tox.23001

关键词

DNA methylation; miR-17-5p; neurotoxicity; paraquat; ROS

资金

  1. Joint Funds for the innovation of science and Technology, Fujian province [2017Y9105]
  2. National Natural Science Foundation of China [81573195, 81903352, 81973083]
  3. Provincial Natural Science Foundation in Fujian [2017J01523]

向作者/读者索取更多资源

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.

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