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

Jamunarani Veeraraghavan, Mohan Natarajan, Terence S. Herman, Natarajan Aravindan

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)44-55
Number of pages12
JournalMutation Research - Genetic Toxicology and Environmental Mutagenesis
Volume718
Issue number1-2
DOIs
StatePublished - Jan 11 2011

Keywords

  • Gene expression
  • Low-dose radiation
  • NFκB
  • Oxidative stress
  • SOD2

ASJC Scopus subject areas

  • Genetics
  • Health, Toxicology and Mutagenesis

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