title: Low-dose radiation activates Nrf1/2 through reactive species and the Ca(2+)/ERK1/2 signaling pathway in human skin fibroblast cells.
abstract: 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.
authors.affiliation: Research Center, Dongnam Institute of Radiological and Medical Science, Busan 619-953.
authors.forename: Eun Kyeong
authors.initials: EK
authors.lastname: Lee
authors.forename: Jin-Ah
authors.initials: JA
authors.lastname: Kim
authors.forename: Seong Joon
authors.initials: SJ
authors.lastname: Park
authors.forename: Jeung Ki
authors.initials: JK
authors.lastname: Kim
authors.forename: Kyu
authors.initials: K
authors.lastname: Heo
authors.forename: Kwang Mo
authors.initials: KM
authors.lastname: Yang
authors.forename: Tae Gen
authors.initials: TG
authors.lastname: Son
mesh_terms: D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation / Q000528:radiation effects; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects*; D006801:Humans; D007477:Ions; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000528:radiation effects*; D012867:Skin / Q000166:cytology / Q000528:radiation effects
chemical_list: D007477:Ions; D051267:NF-E2-Related Factor 2; D017382:Reactive Oxygen Species; D002118:Calcium