Dysfunction of Nrf2 decreases KBrO3-induced oxidative DNA damage in Ogg1-null mice

Paweł Jałoszyński, Soichiro Murata, Yasuhiro Shinkai, Satoru Takahashi, Yoshito Kumagai, Susumu Nishimura, Masayuki Yamamoto

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

Transcription factor Nrf2 regulates production of antioxidants and protects cells from oxidative/electrophilic stresses. Paradoxically, glutathione, one of the Nrf2-regulated antioxidants, has been assumed to promote genotoxicity of KBrO3. To address this glutathione hypothesis, we examined roles Nrf2 plays in the cellular defense against KBrO3-induced oxidative damage using Nrf2-/-, Ogg1-/- and Nrf2::Ogg1 double knockout mice. We found that upon KBrO3 treatment Nrf2::Ogg1 double knockout animals suffered from severe kidney damage, but unexpectedly the double knockout mice accumulated lower level of 8-hydroxyguanine than Ogg1-/- mice. Thus, KBrO3-induced nephrotoxicity appears not to depend on the formation of 8-hydroxyguanine. Our data also indicate that both the KBrO3-induced nephrotoxicity and formation of 8-hydroxyguanine are Nrf2-controlled processes, but the changes of the glutathione level are Nrf2-independent. Based on these results we conclude that glutathione is a minor part of the mechanism promoting genotoxicity of KBrO3 in Ogg1 knockout mice.

Original languageEnglish
Pages (from-to)966-971
Number of pages6
JournalBiochemical and biophysical research communications
Volume364
Issue number4
DOIs
Publication statusPublished - 2007 Dec 28

Keywords

  • 8-oxoguanine
  • Bromate
  • GSH
  • Nrf2
  • Ogg1
  • Oxidative DNA damage
  • Oxidative stress

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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