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

Dysfunction of Nrf2 decreases KBrO3-induced oxidative DNA damage in Ogg1-null mice. Research Abstract Details 

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Dysfunction of Nrf2 decreases KBrO3-induced oxidative DNA damage in Ogg1-null mice. Abstract Text:

Pawe? Ja?oszy?ski,Soichiro Murata,Yasuhiro Shinkai,Satoru Takahashi,Yoshito Kumagai,Susumu Nishimura,Masayuki Yamamoto,Pawe? Ja?oszy?ski,Soichiro Murata,Yasuhiro Shinkai,Satoru Takahashi,Yoshito Kumagai,Susumu Nishimura,Masayuki Yamamoto,

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.

Dysfunction of Nrf2 decreases KBrO3-induced oxidative DNA damage in Ogg1-null mice. Publishing Authors By Initials

P Ja?oszy?ski,S Murata,Y Shinkai,S Takahashi,Y Kumagai,S Nishimura,M Yamamoto,P Ja?oszy?ski,S Murata,Y Shinkai,S Takahashi,Y Kumagai,S Nishimura,M Yamamoto,

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Dysfunction of Nrf2 decreases KBrO3-induced oxidative DNA damage in Ogg1-null mice. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Biochemical and biophysical research communication

VOLUME: 364

Page Numbers: 966-71

Journal Abbreviation: Biochem. Biophys. Res. Commun.

ISSN: 1090-2104

DAY: 29

MONTH: 10

YEAR: 2007

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

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LANGUAGE: eng

NlmUniqueID: 372516

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AFFILIATION: Center for Tsukuba Advanced Research Alliance and JST-ERATO Environmental Response Project, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8577, Japan.

Country: United States

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MEDLINETA: Biochem Biophys Res Commun

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