Related Experiment Video
Updated: Aug 5, 2025

Immunofluorescence Imaging of DNA Damage and Repair Foci in Human Colon Cancer Cells
Published on: June 9, 2020
Stimulation of Nuclear Factor (Erythroid-Derived 2)-like 2 Signaling by Nucleus Targeted Irradiation with Proton
Jun Wang1, Masakazu Oikawa2,3, Teruaki Konishi2
1The Center for Ion Beam Bioengineering and Green Agriculture, Hefei Institute of Physical Science, Chinese Academy of Sciences, Hefei 230031, China.
Abstract:
Nuclear factor (erythroid-derived 2)-like 2 (NRF2), well-known as a master antioxidative response regulator in mammalian cells, is considered as a potential target for radiation protection and cancer therapy sensitization. We examined the response of NRF2 signaling in normal human lung fibroblast WI-38 cells to nucleus targeted irradiation by 3.4 MeV proton microbeam. Nucleus targeted irradiation stimulated the nucleus accumulation of NRF2 and the expression of its target gene, heme oxygenase 1 (HO-1). The nucleus accumulation of NRF2 increased from 3 h to 12 h post 500 proton irradiation. In the 500 protons range, higher number of protons resulted in increased NRF2 nucleus accumulation. Activating NRF2 with tert-butylhydroquinone reduced DNA double-strand break (DSB) formation in nucleus targeted irradiation by 15%. Moreover, ATM phosphorylation was found in nucleus targeted irradiation. Inhibiting ATM with ku55933 prevented NRF2 nucleus accumulation. Furthermore, nucleus targeted irradiation activated ERK 1/2, and ROS-ERK 1/2 signaling regulated NRF2 nucleus accumulation. Taken together, NRF2 signaling was activated by nucleus targeted irradiation and mitigated DNA DSB. The discovery of ATM and ERK 1/2 as upstream regulators of NRF2 signaling in nucleus targeted cells revealed new information regarding radiation protection.
Related Concept Videos
Methods of Nuclear Reprogramming
Introduction to Nuclear Reprogramming
Nuclear Overhauser Enhancement (NOE)
Nucleotide Excision Repair
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Biological Effects of Radiation

