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Oxidative Medicine and Cellular Longevity
Volume 2013, Article ID 848279, 8 pages
Review Article

The Role of the Keap1/Nrf2 Pathway in the Cellular Response to Methylmercury

1Environmental Biology Section, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
2Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan

Received 28 January 2013; Revised 26 May 2013; Accepted 3 June 2013

Academic Editor: Mi-Kyoung Kwak

Copyright © 2013 Yoshito Kumagai et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.