| First Author | Jałoszyński P | Year | 2007 |
| Journal | Biochem Biophys Res Commun | Volume | 364 |
| Issue | 4 | Pages | 966-71 |
| PubMed ID | 17971305 | Mgi Jnum | J:128430 |
| Mgi Id | MGI:3767108 | Doi | 10.1016/j.bbrc.2007.10.123 |
| Citation | Jaloszynski P, et al. (2007) Dysfunction of Nrf2 decreases KBrO3-induced oxidative DNA damage in Ogg1-null mice. Biochem Biophys Res Commun 364(4):966-71 |
| abstractText | 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. |
