title: The role of the Keap1/Nrf2 pathway in the cellular response to methylmercury.
abstract: Methylmercury (MeHg) is an environmental electrophile that covalently modifies cellular proteins with reactive thiols, resulting in the formation of protein adducts. While such protein modifications, referred to as S-mercuration, are thought to be associated with the enzyme dysfunction and cellular damage caused by MeHg exposure, the current consensus is that (1) there is a cellular response to MeHg through the activation of NF-E2-related factor 2 (Nrf2) coupled to S-mercuration of its negative regulator, Kelch-like ECH-associated protein 1 (Keap1), and (2) the Keap1/Nrf2 pathway protects against MeHg toxicity. In this review, we introduce our findings and discuss the observations of other workers concerning the S-mercuration of cellular proteins by MeHg and the importance of the Keap1/Nrf2 pathway in protection against MeHg toxicity in cultured cells and mice.
authors.affiliation: Environmental Biology Section, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Kumagai
authors.forename: Hironori
authors.initials: H
authors.lastname: Kanda
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shinkai
authors.forename: Takashi
authors.initials: T
authors.lastname: Toyama
mesh_terms: D000818:Animals; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D000072019:Kelch-Like ECH-Associated Protein 1; D008767:Methylmercury Compounds / Q000494:pharmacology*; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D008767:Methylmercury Compounds; D051267:NF-E2-Related Factor 2