Low-dose radiation activates Nrf1/2 through reactive species and the Ca2+/ERK1/2 signaling pathway in human skin fibroblast cells
2013
Lee, E.K., Dongnam Institute of Radiological and Medical Science, Busan, Republic of Korea | Kim, J.A., Dongnam Institute of Radiological and Medical Science, Busan, Republic of Korea | Park, S.J., Dongnam Institute of Radiological and Medical Science, Busan, Republic of Korea | Kim, J.K., Dongnam Institute of Radiological and Medical Science, Busan, Republic of Korea | Heo, K., Dongnam Institute of Radiological and Medical Science, Busan, Republic of Korea | Yang, K. M., Dongnam Institute of Radiological and Medical Science, Busan, Republic of Korea | Son, T.G., Dongnam Institute of Radiological and Medical Science, Busan, Republic of Korea
In the current study, we explored the effect of LDR on the activation of Nrfs transcription factor involved in cellular redox events. Experiments were carried out utilizing 0.05 and 0.5 Gy X-ray irradiated normal human skin fibroblast HS27 cells. The results showed LDR induced Nrf1 and Nrf2 activation and expression of antioxidant genes HO-1, Mn-SOD, and NQO1. In particular, 0.05 Gy-irradiation increased only Nrf1 activation, but 0.5 Gy induced both Nrf1 and Nrf2 activation. LDR-mediated Nrf1/2 activation was accompanied by reactive species (RS) generation and Ca2+ flux. This effect was abolished in the presence of N-acetyl-cysteine and BAPTA- AM. Furthermore, Nrf1/2 activation by LDR was suppressed by PD98059, an inhibitor of ERK1/2. In conclusion, LDR induces Nrf1 and Nrf2 activation and expression of Nrf-regulated antioxidant defense genes through RS and Ca2+/ERK1/2 pathways, suggesting new insights into the molecular mechanism underlying the beneficial role of LDR in HS27 cells.
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