Molecular Mechanisms Underlying Cellular Adaptive Response to Low-Dose Radiation
Sponsor: DOE Office of Biological and Environmental Research Low Dose Radiation Research Program
Contact: Colette Sacksteder
The goal of this research is to identify the molecular mechanisms by which cells adapt to low dose radiation exposure. We hypothesize that calmodulin (CaM) and associated signaling complexes are sensors of low-dose radiation, resulting in alterations in energy metabolism and gene expression. Preliminary data demonstrates that CaM expression levels increase linearly with radiation dose, allowing CaM association with low-affinity binding partners such as NFκB family members. This inflammatory response requires the selective degradation of key regulatory proteins (e.g., IκB) by the proteasome, and is dependent on formation of critical proteasome complexes. The sensitivity of CaM to oxidative stress provides additional regulation. We have shown this to be part of an adaptive response that modulates energy metabolism and transcriptional regulation of antioxidant and pro-inflammatory pathways.
To understand such changes in regulatory elements, we are 1) Identifying CaM associated protein complexes as a function of radiation dose, (2) Understanding the role of the proteasome in mediating low-dose adaptive response, and (3) Determining dose-dependent changes in biochemical pathways and associated oxidative modifications of proteins. Knowledge of the exact molecular mechanisms underlying adaptive cellular responses to low-dose radiation is expected to permit more accurate assessments of risk to ionizing radiation.