Low-Dose Gamma-Ray Irradiation Induces Translocation of Nrf2 Into Nuclear in Mouse Macrophage RAW264.7 Cells
Low-Dose Gamma-Ray Irradiation Induces Translocation of Nrf2 Into Nuclear in Mouse Macrophage RAW264.7 Cells
复制标题
DOI：
10.1269/jrr.10002
复制
发表时间：
2010-05-01
影响因子：
2
通讯作者：
Kojima, Shuji
中科院分区：
文献类型：
--
作者：
Tsukimoto, Mitsutoshi;Tamaishi, Nana;Kojima, Shuji
转录因子核红细胞衍生2相关因子2（Nrf 2）调节编码参与细胞氧化还原稳态的抗氧化蛋白的基因表达。而已知γ-射线辐射在体内诱导活性氧物质。虽然已经研究了各种应力对Nrf 2的活化，但尚未确定电离辐射是否诱导Nrf 2的活化。我们研究了小鼠巨噬细胞RAW 264 7细胞中Nrf 2对γ射线照射的响应的活化，用γ射线照射细胞诱导Nrf 2表达的增加，即使0.1戈伊的γ射线照射也是如此。辐射诱导Nrf 2从细胞质易位到细胞核，表明Nrf 2被低剂量辐射激活。血红素加氧酶-1的表达受Nrf 2调节。γ射线剂量大于0.1戈伊时，24 h后的细胞凋亡率也增加。此外，Nrf 2的激活被U 0126抑制。其是细胞外信号调节蛋白激酶1/2（ERK 1/2）途径的抑制剂。提示ERK 1/2依赖性通路参与辐射诱导的Nrf 2激活我们的结果表明，低剂量γ辐射通过ERK 1/2依赖性通路诱导Nrf 2激活
The transcription factor nuclear erythroid-derived 2-related factor 2 (Nrf2) regulates expression of genes encoding antioxidant proteins involved in cellular redox homeostasis. while gamma-ray irradiation is known to induce reactive oxygen species in vivo. Although activation of Nrf2 by various stresses has been studied, it has not yet been determined whether ionizing irradiation induces activation of Nrf2 Therefore, we investigated activation of Nrf2 in response to gamma-irradiation in mouse macrophage RAW264 7 cells Irradiation of cells with gamma-rays induced an increase of Nrf2 expression Even 0 1 Gy of gamma-irradiation induced a translocation of Nrf2 from cytoplasm to the nucleus, indicating the activation of Nrf2 by low-dose irradiation Expression of heme oxygenase-1, which is regulated by Nrf2. was also increased at 24 h after irradiation with more than 0.1 Gy of gamma-rays. Furthermore, the activation of Nrf2 was suppressed by U0126. which is an inhibitor of the extracellular signal regulated protein kinase 1/2 (ERK1/2) pathway. suggesting involvement of ERK1/2-dependent pathway in the irradiation-induced activation of Nrf2 Our results indicate that low-dose gamma-irradiation induces activation of Nrf2 through ERK1/2-dependent pathways