Host: The Japanese Society of Toxicology
Name : The 50th Annual Meeting of the Japanese Society of Toxicology
Date : June 19, 2023 - June 21, 2023
It has been pointed out that dysfunction of the epigenome results in various diseases. However, the mechanism by which the epigenome is regulated remains unclear. We focused on DNA methyltransferase (DNMT), which catalyzes cytosine methylation in the genome. Initially, we investigated the effect of nitric oxide (NO) on DNMT. NO oxidatively modifies (S-nitrosylates) the thiol portion of cysteine residues in various proteins and modulates its enzymatic activity. We examined whether NO induces DNMT S-nitrosylation in vitro and in vivo. S-Nitrosylation of DNMT (SNO-DNMT) formation was observed by treatment with NO donor in a concentration- and time-dependent manner. In addition, the enzymatic activity of DNMT was significantly reduced by exposure to NO. This inhibition resulted in genomic DNA demethylation, which in turn led to various genes expression. This phenomenon may be involved in NO-mediated pathogenesis. We then screened for environmental chemicals with similar effects to NO. Interestingly, some environmental electrophiles inhibited DNMT enzymatic activity via covalent modifications. We will introduce the recent findings on the properties and functions of those compounds.
