Image courtesy of Thomas Weber, Pacific Northwest National Laboratory
Using fluorescence microscopy, researchers observed the location of annexin A2 protein within cells under normal conditions (left) and after irradiation (right), which caused a majority of the proteins to relocate to the nucleus.
Understanding the potential effects of low doses of ionizing radiation on human health requires knowledge of how it influences biology at the tissue level. One key question is how irradiated cells communicate to their neighbors.
These results could lead to new, targeted approaches in therapies directed at regulating radiation-induced cell death.
Scientists at Pacific Northwest National Laboratory are working to define signaling pathways activated by low doses of radiation. Their previous studies found that the protein annexin A2 is involved in the malignant transformation of cultured mouse epidermal cells by radiation. The researchers now demonstrate that both high and low doses of ionizing radiation increase A2 annexin levels in the nuclei of human and mouse monolayer cultures and in a human skin tissue model, thus supporting a conserved nuclear function for annexin A2. Whole-genome expression profiling in the presence and absence of annexin A2 identified altered transcriptional programming that changes the radioresponsive transcriptome. Bioinformatics predicted that silencing A2 may enhance cell death responses to stress associated with reduced activation of survival signals. The researchers validated the prediction by demonstrating that the A2-silenced cells were more likely than control cells to die after treatment with tumor necrosis factor alpha. Collectively, the data suggest that annexin A2 functions to regulate cell fate, which could impact the biological response to radiation.
Thomas J. Weber
Cell Biology and Biochemistry, Pacific Northwest National Laboratory, 902 Battelle Blvd., J4-02, Richland, WA 99352
This work was supported by the Office of Biological and Environmental Research (BER) within the U.S. Department of Energy (DE-AC06-76RLO) and the National Aeronautics and Space Administration (NNX10AB06G).
Waters, K.M., et al. “Annexin A2 modulates radiation-sensitive transcriptional programming and cell fate.” Radiat. Res. 179, 53–61 (2013). [DOI: 10.1667/RR3056.1].