PUBLICATION

H2O2/DEM-Promoted Maft Promoter Demethylation Drives Nrf2/ARE Activation in Zebrafish

Authors
Chen, C., He, M., Li, X., Yu, L., Liu, Y., Yang, Y., Li, L., Jia, J., Li, B.
ID
ZDB-PUB-220924-25
Date
2022
Source
Life (Basel, Switzerland)   12(9): (Journal)
Registered Authors
Li, Li
Keywords
Nrf2/ARE signaling pathway, methylation regulation, oxidative stress, zebrafish
MeSH Terms
none
PubMed
36143473 Full text @ Life (Basel)
Citation
Chen, C., He, M., Li, X., Yu, L., Liu, Y., Yang, Y., Li, L., Jia, J., Li, B. (2022) H2O2/DEM-Promoted Maft Promoter Demethylation Drives Nrf2/ARE Activation in Zebrafish. Life (Basel, Switzerland). 12(9).
Abstract
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 (H2O2) and Diethyl Maleate (DEM) activated the Nrf2/ARE signaling pathway at 120 hpf in zebrafish. H2O2 regulated the demethylation of the maft promoter by inhibiting the expression of methyltransferase. This promotes the mRNA expression of the Nrf2 binding factor maft, 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 maft. It activated the expression of the maft, further improving the Nrf2/ARE signal pathway. At last, antioxidant target genes were activated. It was shown that H2O2 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.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
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