H<sub>2</sub>O<sub>2</sub>/DEM-Promoted <i>Maft</i> Promoter Demethylation Drives Nrf2/ARE Activation in Zebrafish
The Nrf2/ARE signaling pathway is a cell survival response pathway in response to environmental stresses. The Nrf2/ARE signaling pathway can be activated by stimulating cysteine residues at different positions in the Keap1. However, the epigenetic mechanisms of the Nrf2/ARE pathway under different s...
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MDPI AG
2022-09-01
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| author | Ce Chen Mingyue He Xueting Li Lidong Yu Yi Liu Yan Yang Li Li Jianbo Jia Bingsheng Li |
| author_facet | Ce Chen Mingyue He Xueting Li Lidong Yu Yi Liu Yan Yang Li Li Jianbo Jia Bingsheng Li |
| author_sort | Ce Chen |
| collection | DOAJ |
| description | The Nrf2/ARE signaling pathway is a cell survival response pathway in response to environmental stresses. The Nrf2/ARE signaling pathway can be activated by stimulating cysteine residues at different positions in the Keap1. However, the epigenetic mechanisms of the Nrf2/ARE pathway under different stimuli are still poorly understood. In this study, we found that both hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) and Diethyl Maleate (DEM) activated the Nrf2/ARE signaling pathway at 120 hpf in zebrafish. H<sub>2</sub>O<sub>2</sub> regulated the demethylation of the <i>maft</i> promoter by inhibiting the expression of methyltransferase. This promotes the mRNA expression of the Nrf2 binding factor <i>maft</i>, thereby promoting the downstream antioxidant genes. The methylation of the Nrf2/ARE signaling pathway was not significantly regulated by DEM. However, under oxidative stress, the methyltransferase inhibitors (decitabine and azacitidine) demethylated the promoter region of <i>maft</i>. It activated the expression of the <i>maft</i>, further improving the Nrf2/ARE signal pathway. At last, antioxidant target genes were activated. It was shown that H<sub>2</sub>O<sub>2</sub> and DEM cooperated with methyltransferase inhibitors, providing an important reference for the treatment of oxidative stress-related diseases and breaking new ground for the study of the mechanism of methyltransferase inhibitors in the process of tumor chemotherapy. |
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| spelling | doaj.art-f3e65be5274f410b89eed3f8ce7040c42023-11-23T17:24:08ZengMDPI AGLife2075-17292022-09-01129143610.3390/life12091436H<sub>2</sub>O<sub>2</sub>/DEM-Promoted <i>Maft</i> Promoter Demethylation Drives Nrf2/ARE Activation in ZebrafishCe Chen0Mingyue He1Xueting Li2Lidong Yu3Yi Liu4Yan Yang5Li Li6Jianbo Jia7Bingsheng Li8School of Life Science and Technology, Harbin Institute of Technology, Harbin 150080, ChinaSchool of Life Science and Technology, Harbin Institute of Technology, Harbin 150080, ChinaSchool of Life Science and Technology, Harbin Institute of Technology, Harbin 150080, ChinaSchool of Physics, Harbin Institute of Technology, Harbin 150080, ChinaSchool of Life Science and Technology, Harbin Institute of Technology, Harbin 150080, ChinaSchool of Life Science and Technology, Harbin Institute of Technology, Harbin 150080, ChinaSchool of Life Science and Technology, Harbin Institute of Technology, Harbin 150080, ChinaSchool of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, ChinaKey Laboratory of UV Light Emitting Materials and Technology of Ministry of Education, Northeast Normal University, Changchun 130024, ChinaThe Nrf2/ARE signaling pathway is a cell survival response pathway in response to environmental stresses. The Nrf2/ARE signaling pathway can be activated by stimulating cysteine residues at different positions in the Keap1. However, the epigenetic mechanisms of the Nrf2/ARE pathway under different stimuli are still poorly understood. In this study, we found that both hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) and Diethyl Maleate (DEM) activated the Nrf2/ARE signaling pathway at 120 hpf in zebrafish. H<sub>2</sub>O<sub>2</sub> regulated the demethylation of the <i>maft</i> promoter by inhibiting the expression of methyltransferase. This promotes the mRNA expression of the Nrf2 binding factor <i>maft</i>, thereby promoting the downstream antioxidant genes. The methylation of the Nrf2/ARE signaling pathway was not significantly regulated by DEM. However, under oxidative stress, the methyltransferase inhibitors (decitabine and azacitidine) demethylated the promoter region of <i>maft</i>. It activated the expression of the <i>maft</i>, further improving the Nrf2/ARE signal pathway. At last, antioxidant target genes were activated. It was shown that H<sub>2</sub>O<sub>2</sub> and DEM cooperated with methyltransferase inhibitors, providing an important reference for the treatment of oxidative stress-related diseases and breaking new ground for the study of the mechanism of methyltransferase inhibitors in the process of tumor chemotherapy.https://www.mdpi.com/2075-1729/12/9/1436zebrafishNrf2/ARE signaling pathwayoxidative stressmethylation regulation |
| spellingShingle | Ce Chen Mingyue He Xueting Li Lidong Yu Yi Liu Yan Yang Li Li Jianbo Jia Bingsheng Li H<sub>2</sub>O<sub>2</sub>/DEM-Promoted <i>Maft</i> Promoter Demethylation Drives Nrf2/ARE Activation in Zebrafish Life zebrafish Nrf2/ARE signaling pathway oxidative stress methylation regulation |
| title | H<sub>2</sub>O<sub>2</sub>/DEM-Promoted <i>Maft</i> Promoter Demethylation Drives Nrf2/ARE Activation in Zebrafish |
| title_full | H<sub>2</sub>O<sub>2</sub>/DEM-Promoted <i>Maft</i> Promoter Demethylation Drives Nrf2/ARE Activation in Zebrafish |
| title_fullStr | H<sub>2</sub>O<sub>2</sub>/DEM-Promoted <i>Maft</i> Promoter Demethylation Drives Nrf2/ARE Activation in Zebrafish |
| title_full_unstemmed | H<sub>2</sub>O<sub>2</sub>/DEM-Promoted <i>Maft</i> Promoter Demethylation Drives Nrf2/ARE Activation in Zebrafish |
| title_short | H<sub>2</sub>O<sub>2</sub>/DEM-Promoted <i>Maft</i> Promoter Demethylation Drives Nrf2/ARE Activation in Zebrafish |
| title_sort | h sub 2 sub o sub 2 sub dem promoted i maft i promoter demethylation drives nrf2 are activation in zebrafish |
| topic | zebrafish Nrf2/ARE signaling pathway oxidative stress methylation regulation |
| url | https://www.mdpi.com/2075-1729/12/9/1436 |
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