Cytoprotective role of Nrf2/Keap1 system in methylmercury toxicity

Takashi Toyama, Daigo Sumi, Yasuhiro Shinkai, Akira Yasutake, Keiko Taguchi, Kit I. Tong, Masayuki Yamamoto, Yoshito Kumagai

Research output: Contribution to journalArticlepeer-review

98 Citations (Scopus)

Abstract

Human exposure to methylmercury (MeHg) from contaminated fish is a potential health risk. Because of its chemical properties as a soft electrophile, we investigated the participation of Nrf2 in the cellular response to and protection against MeHg with SH-SY5Y cells and with primary mouse hepatocytes from Nrf2- and Keap1-deficient mice. Exposure of SH-SY5Y cells to MeHg activated Nrf2 through the binding of MeHg and Keap1. Nrf2 overexpression attenuated MeHg-induced cytotoxicity in SH-SY5Y cells. In addition, primary mouse hepatocytes extracted from Nrf2-deficient mouse was susceptible, and hepatocyte-specific conditional Keap1-deficient mouse was resistant to MeHg-induced cytotoxicity. Consistent with this data, MeHg was accumulated by Nrf2 deficiency and reduced by Keap1 deficiency. Our findings indicate that MeHg activates Nrf2 and the activation of Nrf2 is essential for reduction of MeHg toxicity by facilitating its excretion into extracellular space.

Original languageEnglish
Pages (from-to)645-650
Number of pages6
JournalBiochemical and biophysical research communications
Volume363
Issue number3
DOIs
Publication statusPublished - 2007 Nov 23
Externally publishedYes

Keywords

  • Cyototoxicity
  • Electrophile
  • Keap1
  • Methylmercury
  • Nrf2

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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