KMID : 0624620130460050258
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BMB Reports 2013 Volume.46 No. 5 p.258 ~ p.263
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Low-dose radiation activates Nrf1/2 through reactive species and the Ca2+/ERK1/2 signaling pathway in human skin fibroblast cells
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Lee Eun-Kyeong
Kim Jin-Ah Park Seong-Joon Kim Jeung-Ki Heo Kyu Yang Kwang-Mo Son Tae-Gen
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Abstract
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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 Ca(2+) 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 Ca(2+)/ERK1/2 pathways, suggesting new insights into the molecular mechanism underlying the beneficial role of LDR in HS27 cells.
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KEYWORD
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Ca2+, ERK1/2, Nrf1/2, Reactive species, X-ray
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