血红素加氧酶-1在低剂量辐射适应性反应中的作用。
Role of heme Oxygenase-1 in low dose Radioadaptive response.
作者信息
Bao Lingzhi, Ma Jie, Chen Guodong, Hou Jue, Hei Tom K, Yu K N, Han Wei
机构信息
Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China.
Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China; University of Science and Technology of China, Hefei, Anhui, China.
出版信息
Redox Biol. 2016 Aug;8:333-40. doi: 10.1016/j.redox.2016.03.002. Epub 2016 Mar 3.
Radioadaptive response (RAR) is an important phenomenon induced by low dose radiation. However, the molecular mechanism of RAR is obscure. In this study, we focused on the possible role of heme oxygenase 1 (HO-1) in RAR. Consistent with previous studies, priming dose of X-ray radiation (1-10cGy) induced significant RAR in normal human skin fibroblasts (AG 1522 cells). Transcription and translation of HO-1 was up-regulated more than two fold by a priming dose of radiation (5cGy). Zinc protoporphyrin Ⅸ, a specific competitive inhibitor of HO-1, efficiently inhibited RAR whereas hemin, an inducer of HO-1, could mimic priming dose of X-rays to induce RAR. Knocking down of HO-1 by transfection of HO-1 siRNA significantly attenuated RAR. Furthermore, the expression of HO-1 gene was modulated by the nuclear factor (erythroid-derived 2)-like 2 (Nrf2), which translocated from cytoplasm to nucleus after priming dose radiation and enhance the antioxidant level of cells.
辐射适应性反应（RAR）是低剂量辐射诱导产生的一种重要现象。然而，RAR的分子机制尚不清楚。在本研究中，我们重点关注了血红素加氧酶1（HO-1）在RAR中可能发挥的作用。与之前的研究一致，低剂量X射线辐射（1-10cGy）可在正常人皮肤成纤维细胞（AG 1522细胞）中诱导出显著的RAR。低剂量辐射（5cGy）可使HO-1的转录和翻译上调两倍以上。HO-1的特异性竞争性抑制剂锌原卟啉Ⅸ能有效抑制RAR，而HO-1的诱导剂血红素则可模拟低剂量X射线诱导RAR。通过转染HO-1 siRNA敲低HO-1可显著减弱RAR。此外，HO-1基因的表达受核因子（红细胞衍生2）样2（Nrf2）调控，低剂量辐射后Nrf2从细胞质转位至细胞核，从而提高细胞的抗氧化水平。
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