Response of the Nrf2 protection system in human monocytic cells after ionising irradiation

Abstract

In response to reactive oxygen species (ROS) or electrophiles, the transcription factor nuclear factor-erythroid 2 (NF-E2)-related factor 2 (Nrf2) rapidly translocates into the nucleus and induces the expression of various antioxidant genes, such as heme oxygenase-1 (HO-1). Low linear energy transfer (LET) ionising radiations such as X-rays generate ROS, which cause biological damage. However, little is known about whether the Nrf2 system in human monocytic cells is activated by low LET ionising irradiation. Therefore, in this study, the response of the Nrf2 system to X-irradiation in human monocytic THP1 cells was investigated. Following exposure of THP1 cells to X-rays (1-5 Gy), intracellular ROS levels were measured using 2',7'-dichlorodihydrofluorescein diacetate, Nrf2 localisation was determined using immunofluorescence staining and HO-1 mRNA and protein expression were examined. Although ROS were generated by irradiation in a dose-dependent manner, they disappeared immediately after irradiation. Nrf2 translocation into the nucleus was observed 6 h after 5 Gy X-irradiation but was not detected following 1-2 Gy irradiation or in non-irradiated controls. HO-1 expression was significantly higher in 5 Gy-irradiated cells after 24 h than in non-irradiated controls. These results indicate that high-dose irradiation (5 Gy) activates Nrf2 and that the Nrf2 protection system may function from 24 h after irradiation in human monocytic cells.