Involvement of ERK-Nrf-2 Signaling in Ionizing Radiation Induced Cell Death in Normal and Tumor Cells

摘要: Prolonged oxidative stress favors tumorigenic environment and inflammation. Oxidative may trigger redox adaptation mechanism(s) in tumor cells but not normal cells. This increase levels of intracellular antioxidants establish a new homeostasis. Nrf-2, master regulator battery antioxidant genes is constitutively activated many Here we show that, murine T cell lymphoma EL-4 constitutive inducible radioresistance via activation Nrf-2/ERK pathway. contained lower ROS than their counterpart splenic lymphocytes. In response to radiation, the thiol circuits, GSH thioredoxin were modified Pharmacological inhibitors ERK Nrf-2 significantly enhanced radiosensitivity reduced clonogenic potential Unirradiated showed nuclear accumulation upregulation its dependent protein levels. Interestingly, MEK inhibitor abrogated translocation suggesting role basal radiation induced Double knockdown resulted higher sensitivity death as compared individual Importantly, NF-kB which reported be active tumors was present at inhibition did influence Thus our results reveal are subjected heightened employ cellular homeostasis for prevention death. Our study reveals molecular basis highlights ERK.