Molecular Mechanisms Underlying Cellular Adaptive Response to Low Dose Radiation
EMSL Project ID
14100
Abstract
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 NFĸB family members. This inflammatory response requires the selective degradation of key regulatory proteins (e.g. IĸB) 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 propose three specific aims: (1) Identify CaM associated protein complexes as a function of radiation dose, (2) Understand the role of the proteasome in mediating low-dose adaptive response, and (3) Determine 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.
Project Details
Start Date
2005-04-20
End Date
2008-04-20
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members