Low-dose γ-radiation-induced oxidative stress response in mouse brain and gut: Regulation by NFκB-MnSOD cross-signaling

Radiation-induced amplification of reactive oxygen species (ROS) may be a sensing mechanism for activation of signaling cascades that influence cell fate. However, the regulated intrinsic mechanisms and targets of low-dose ionizing radiation (LDIR) are still unclear. Accordingly, we investigated the effects of LDIR on NF kappa B signal transduction and manganese superoxide dismutase (SOD2) activity in mice brain and gut. LDIR resulted in both dose-dependent and persistent NF kappa B activation in gut and brain. QPCR displayed a dose- and tissue-dependent differential modulation of 88 signaling molecules. With stringent criteria, a total of 15 (2 cGy), 43 (10 cGy) and 19 (50 cGy) genes were found to be commonly upregulated between brain and gut. SOD2 immunostaining showed a LDIR-dose dependent increase. Consistent with the NF kappa B results, we observed a persistent increase in SOD2 activity after LDIR. Moreover, muting of LDIR-induced NF kappa B attenuated SOD2 transactivation and cellular localization. These results imply that exposure of healthy tissues to LDIR results in induced NF kappa B and SOD2 activity and transcriptional activation of NF kappa B-signal transduction/target molecules. More importantly, the results suggest that NF kappa B initiates a feedback response through transcriptional activation of SOD2 that may play a key role in the LDIR-induced oxidative stress response and may control the switch that directs cell fate. (C) 2010 Elsevier B.V. All rights reserved.