Pi class glutathione S-transferase genes are regulated by Nrf2 through an evolutionarily conserved regulatory element in zebrafish

Takafumi Suzuki, Yaeko Takagi, Hitoshi Osanai, L. I. Li, Miki Takeuchi, Yasutake Katoh, Makoto Kobayashi, Masayuki Yamamoto

Research output: Contribution to journalArticlepeer-review

80 Citations (Scopus)

Abstract

Pi class GSTs (glutathione S-transferases) are a member of the vertebrate GST family of proteins that catalyse the conjugation of GSH to electrophilic compounds. The expression of Pi class GST genes can be induced by exposure to electrophiles. We demonstrated previously that the transcription factor Nrf2 (NF-E2 p45-related factor 2) mediates this induction, not only in mammals, but also in fish. In the present study, we have isolated the genomic region of zebrafish containing the genes gstp1 and gstp2. The regulatory regions of zebrafish gstp1 and gstp2 have been examined by GFP (green fluorescent protein)-reporter gene analyses using microinjection into zebrafish embryos. Deletion and point-mutation analyses of the gstp1 promoter showed that an ARE (antioxidant-responsive element)-like sequence is located 50 bp upstream of the transcription initiation site which is essential for Nrf 2 transactivation. Using EMSA (electrophoretic mobility-shift assay) analysis we showed that zebrafish Nrf 2-MafK heterodimer specifically bound to this sequence. All the vertebrate Pi class GST genes harbour a similar ARE-like sequence in their promoter regions. We propose that this sequence is a conserved target site for Nrf 2 in the Pi class GST genes.

Original languageEnglish
Pages (from-to)65-73
Number of pages9
JournalBiochemical Journal
Volume388
Issue number1
DOIs
Publication statusPublished - 2005 May 15
Externally publishedYes

Keywords

  • Antioxidant-responsive element (ARE)
  • Gene transcription
  • Glutathione S-transferase (GST)
  • Green fluorescent protein (GFP)
  • Phase 2 detoxification enzyme
  • Pi class glutathione S-transferase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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