Low-dose radiation activates Nrf1/2 through reactive species and the Ca(2+)/ERK1/2 signaling pathway in human skin fibroblast cells

BMB Rep. 2013 May;46(5):258-63. doi: 10.5483/bmbrep.2013.46.5.199.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / metabolism*
  • Cell Line
  • Cell Proliferation / radiation effects
  • Fibroblasts / metabolism
  • Fibroblasts / radiation effects*
  • Humans
  • Ions
  • MAP Kinase Signaling System / physiology*
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism*
  • NF-E2-Related Factor 2 / radiation effects*
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction / radiation effects*
  • Skin / cytology
  • Skin / radiation effects


  • Ions
  • NF-E2-Related Factor 2
  • Reactive Oxygen Species
  • Calcium