The Role of Nrf2 in the Response to Normal Tissue Radiation Injury.

The Role of Nrf2 in the Response to Normal Tissue Radiation Injury. Radiat Res. 2018 May 25;: Authors: Cameron BD, Sekhar KR, Ofori M, Freeman ML Abstract The transcription factor Nrf2 is an important modulator of antioxidant and drug metabolism, carbohydrate and lipid metabolism, as well as heme and iron metabolism. Regulation of Nrf2 expression occurs transcriptionally and post-transcriptionally. Post-transcriptional regulation entails ubiquitination followed by proteasome-dependent degradation. Additionally, Nrf2-mediated gene expression is subject to negative regulation by ATF3, Bach1 and cMyc. Nrf2-mediated gene expression is an important regulator of a cell's response to radiation. A majority of studies have shown that Nrf2-deficient cells are radiosensitized while Nrf2 overexpression confers radioresistance. Consistent with this knowledge, which is shown in the literature, the Nrf2 activator CDDO attenuated radiation-mediated crypt injury. However, in another study of Nrf2-null mice, intestinal crypts were unexpectedly found to be radioresistant compared to wild-type crypts. Further investigation is needed to define the relationship between Nrf2 and radiation sensitivity in Lgr5+ and Bim1+ cells that regulate regeneration of crypt stem cells. In hematopoietic compartments Nrf2 promotes the survival of irradiated osteoblasts that support long-term hematopoietic stem cell (LT-HSC) niches. Loss of Nrf2 in LT-HSCs increases stem c...
Source: Radiation Research - Category: Physics Authors: Tags: Radiat Res Source Type: research