Global Quantitative Proteomics of Irradiated Nrf2 Knockout Mus for Biomarker Discovery

摘要

Radiation therapy, which is commonly used for the treatment of many cancers, exposes the tissue to excessive amounts of free radicals and compels the overexpression of antioxidant genes. The transcription factor NF-E2-related factor 2 (Nrf2) plays a key role in natural antioxidant systems by binding to antioxidant DNA response element (ARE) and upregulating ARE-dependent cytoprotective genes to combat oxidative stress. This study was designed to investigate the proteomic changes over a time course in serum of Nrf2 deficient Mus exposed to radiation. In addition, Nrf2-KO mouse embryonic fibroblasts (MEF) subjected to tert-butylhydroquinone (tBHQ) drug therapy were analyzed to observe regulation of cytoprotective proteins as a result from the antioxidative properties of tBHQ. Through the use of isotopic reductive methylation, we were able to relatively quantitate murine protein species against time and extrapolate on the Nrf2-ARE pathway.