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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초록
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+/ERK1/2pathways, suggesting new insights into the molecular mechanism underlying the beneficial role of LDR in HS27cells.
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 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+/ERK1/2pathways, suggesting new insights into the molecular mechanism underlying the beneficial role of LDR in HS27cells.
참고문헌 (24)
- Gori, T., "Biological effects of low-dose radiation: of harm and hormesis", Eur. Heart J, 33, pp.292~295 (2012)
- Liang, X., "The low-dose ionizing radiation stimulates cell proliferation via activation of the MAPK", ERK pathway in rat cultured mesenchymal stem cells, 2011, pp.52, 380~386
- Ahmed, K. M., "Coactivation of ATM", ERK, Free Radic. Biol. Med, pp.2009, 46[DOI]
- Moskalev, A. A., "Radiation hormesis and radioadaptive response in Drosophila melanogaster flies with different genetic backgrounds: the role of cellular stress-resistance mechanisms", Biogerontology, 12, pp.253~263 (2011)
- Seong, K. M., "Genome-wide analysis of low-dose irradiated male Drosophila melanogaster with extended longevity", Biogerontology, 12, pp.93~107 (2011)
- Ina, Y., "Activation of immunological network by chronic low-dose-rate irradiation in wild-type mouse strains: analysis of immune cell populations and surface molecules", Int. J. Radiat. Biol, 81, pp.721~729 (2005)
- Hashimoto, S., "The suppression of metastases and the change in host immune response after low-dose total-body irradiation in tumor-bearing rats", Radiat. Res, 151, pp.717~724 (1999)
- Takahashi, M., "Prevention of type I diabetes by low-dose gamma irradiation in NOD mice", Radiat. Res, 154, pp.680~685 (2000)
- Rödel, F., "Dose-dependent biphasic induction and transcriptional activity of nuclear factor kappa B (NF-kappaB) in EA.hy.926 endothelial cells after low-dose X-irradiation", Int. J. Radiat. Biol, 80, pp.115~232 (2004)
- Kawakita, Y., "Increase of intracellular glutathione by low-dose gamma-ray irradiation is mediated by transcription factor AP-1 in RAW 264.7 cells", Biol. Pharm. Bull, 26, pp.19~23 (2003)
- Zhang, Q., "A systems biology perspective on Nrf2-mediated antioxidant response", Toxicol. Appl. Pharmacol, 244, pp.84~97 (2010)
- Kobayashi, M., "Molecular mechanisms activating the Nrf2-Keap1 pathway of antioxidant gene regulation", Antioxid. Redox Signal, 7, pp.385~394 (2005)
- Kaspar, J. W., "Nrf2:INrf2 (Keap1) signaling in oxidative stress", Free Radic. Biol. Med, 47, pp.1304~1309 (2009)
- Tsukimoto, M., "Low-dose gamma-ray irradiation induces translocation of Nrf2 into nuclear in mouse macrophage RAW264.7 cells", J. Radiat. Res. (Tokyo), 51, pp.349~353 (2010)
- Corre, I., "Plasma membrane signaling induced by ionizing radiation", Mutat. Res, 704, pp.61~67 (2010)
- Kim, A. N., "Up-regulation of heme oxygenase-1 expression through CaMKII- RK1", 2-Nrf2 signaling mediates the anti-inflammatory effect of bisdemethoxycurcumin in LPS-stimulated macrophages, 2010, pp.49, 323~331
- Xu, C., "Mechanism of action of isothiocyanates: the induction of ARE-regulated genes is associated with activation of ERK and JNK and the phosphorylation and nuclear translocation of Nrf2", Mol. Cancer Ther, 5, pp.1918~1926 (2006)
- Ohtsuji, M., "Nrf1 and Nrf2 play distinct roles in activation of antioxidant response element- dependent genes", J. Biol. Chem, 283, pp.33554~33562 (2008)
- Kojima, S., "Elevation of antioxidant potency in the brain of mice by low-dose gamma-ray irradiation and its effect on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced brain damage", Free Radic. Biol. Med, 26, pp.388~395 (1999)
- Yamaoka, K., "Change of glutathione peroxidase synthesis along with that of superoxide dismutase synthesis in mice spleens after low-dose X-ray irradiation", Biochim. Biophys. Acta, 1381, pp.265~270 (1998)
- Raaphorst, G. P., "Adaptive response and its variation in human normal and tumour cells", Int. J. Radiat. Biol, 75, pp.865~873 (1999)
- Kim, C. S., "Low-dose of ionizing radiation enhances cell proliferation via transient ERK1", 2 and p38 activation in normal human lung fibroblasts, 2007, pp.48, 407~415
- Keum, Y. S., "Chemoprevention by isothiocyanates and their underlying molecular signaling mechanisms", Mutat. Res, 555, pp.191~202 (2004)
- Korystov, Y. N., "Detection of reactive oxygen species induced by radiation in cells using the dichlorofluorescein assay", Radiat. Res, 168, pp.226~232 (2007)