環境中親電子物質エクスポソームのモデル化

抄録

We are exposed to numerous xenobiotic electrophiles on a daily basis through living environment, lifestyle, and dietary habits. Such reactive substances are reported to covalently modify protein thiols, resulting in formation of protein adducts. We found that xenobiotic electrophiles activate a variety of redox signaling pathways through selective modification of sensor proteins at low dose and cause disruption of the signaling and toxicity through non-selective and extensive modification of cellular proteins at high dose. We also found that reactive sulfur species (e.g., cysteine persulfide, glutathione (GSH) persulfide, hydrogen sulfide) are able to capture xenobiotic electrophiles, leading to formation of their sulfur adducts, thereby inactivating these electrophiles. Furthermore, it was demonstrated that nuclear factor-erythroid 2-related factor 2 (Nrf2) and cystathionine gamma-lyase (CSE) are involved in decreased risk of electrophilic stress in parallel through GSH and sulfur adduct formation, respectively. By the way, the concept of "exposome", which is the totality of exposure, has been proposed and has become a hot topic. In this symposium, I introduce the methodology using environmental electrophiles as a model of restricted exposome.