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 NFκB signal transduction and manganese superoxide dismutase (SOD2) activity in mice brain and gut. LDIR resulted in both dose-dependent and persistent NFκB 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 (2cGy), 43 (10cGy) and 19 (50cGy) genes were found to be commonly upregulated between brain and gut. SOD2 immunostaining showed a LDIR-dose dependent increase. Consistent with the NFκB results, we observed a persistent increase in SOD2 activity after LDIR. Moreover, muting of LDIR-induced NFκB attenuated SOD2 transactivation and cellular localization. These results imply that exposure of healthy tissues to LDIR results in induced NFκB and SOD2 activity and transcriptional activation of NFκB-signal transduction/target molecules. More importantly, the results suggest that NFκB 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.
Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Jamunarani
J
Veeraraghavan
Mohan
M
Natarajan
Terence S
TS
Herman
Natarajan
N
Aravindan
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism* / Q000528:radiation effects*; D017931:DNA Primers / Q000235:genetics; D004064:Digestive System / Q000187:drug effects* / Q000378:metabolism*; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays / Q000009:adverse effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000528:radiation effects; D016133:Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000528:radiation effects; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000528:radiation effects; D000099156:Superoxide Dismutase 2
D017931:DNA Primers; D016328:NF-kappa B; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2