TY - JOUR
T1 - Low-dose γ-radiation-induced oxidative stress response in mouse brain and gut
T2 - Regulation by NFκB-MnSOD cross-signaling
AU - Veeraraghavan, Jamunarani
AU - Natarajan, Mohan
AU - Herman, Terence S.
AU - Aravindan, Natarajan
N1 - Funding Information:
This work was supported by a Presbyterian Health Foundation seed grant; American Cancer Society ACS-IRG-05-066-0; Department of Radiation Oncology research development funds to Natarajan Aravindan, and Office of Science (BER), US Department of Energy: DE-FG02-03ER63449 funding to Mohan Natarajan.
PY - 2011/1/11
Y1 - 2011/1/11
N2 - 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 (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 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.
AB - 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 (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 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.
KW - Gene expression
KW - Low-dose radiation
KW - NFκB
KW - Oxidative stress
KW - SOD2
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U2 - 10.1016/j.mrgentox.2010.10.006
DO - 10.1016/j.mrgentox.2010.10.006
M3 - Article
C2 - 21056117
AN - SCOPUS:78650171560
SN - 1383-5718
VL - 718
SP - 44
EP - 55
JO - Mutation Research - Genetic Toxicology and Environmental Mutagenesis
JF - Mutation Research - Genetic Toxicology and Environmental Mutagenesis
IS - 1-2
ER -