Induction of endogenous Nrf2/Small maf heterodimers by arsenic-mediated stress in placental choriocarcinoma cells
Induction of endogenous Nrf2/Small maf heterodimers by arsenic-mediated stress in placental choriocarcinoma cells
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DOI：
10.1089/ars.2006.8.53
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发表时间：
2006-01-01
影响因子：
6.6
通讯作者：
Blank, V
中科院分区：
文献类型：
--
作者：
Massrieh, W;Derjuga, A;Blank, V
无机砷暴露与各种癌症、神经系统发病机制和血管疾病以及生殖和发育毒性有关。在这里，无机砷对胎盘绒毛膜癌细胞的影响进行了评估。在砷的存在下，强烈诱导CNC转录因子Nrf 2的核蛋白水平。剂量反应实验表明，0.5 μ M的砷是足以增加Nrf 2水平。Nrf 2二聚化伴侣MafG. MafK似乎不受砷的调节，而MafF蛋白水平略有增加。砷还诱导内源性Nrf 2/小Maf DNA结合复合物与应激反应元件（StRE）识别位点的结合。此外，砷引起的氧化应激在绒毛膜癌细胞模型证明了细胞内H2 0 2水平的增加。血红素加氧酶-1（HO-1），一种已知的Nrf 2靶基因的表达，通过暴露于砷中而上调。这些结果表明，Nrf 2/小Maf异二聚体可能在胎盘细胞对砷介导的应激反应中发挥重要作用。
Exposure to inorganic arsenic has been associated with various forms of cancer, nervous system pathogenesis, and vascular diseases, as well as reproductive and developmental toxicity. Here, the effect of inorganic arsenic on placental JAR choriocarcinoma cells was assessed. The nuclear protein levels of the CNC transcription factor Nrf2 were strongly induced in the presence of arsenic. Dosage response experiments showed that 0.5 mu M of arsenic is sufficient to augment Nrf2 levels. The expression of the Nrf2 dimerization partners MafG. and MafK appeared not to be modulated by arsenic, whereas MafF protein levels were slightly increased. Arsenic also induced the binding of endogenous Nrf2/small Maf DNA-binding complexes to a stress response element (StRE) recognition site. In addition, arsenic caused oxidative stress in the choriocarcinoma cell model as evidenced by an increase in intracellular H 2 0 2 levels. Expression of the enzyme heme oxygenase-1 (HO-1), a known Nrf2 target gene, was upregulated by exposure of JAR cells to arsenic. These results suggest that Nrf2/small Maf heterodimers may play an important role in the response to arsenic-mediated stress in placental cells.