Partial contribution of the Keap1-Nrf2 system to cadmium-mediated metallothionein expression in vascular endothelial cells.
Partial contribution of the Keap1-Nrf2 system to cadmium-mediated metallothionein expression in vascular endothelial cells.
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DOI：
10.1016/j.taap.2016.01.020
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发表时间：
2016-03
影响因子：
3.8
通讯作者：
Y. Shinkai;T. Kimura;Ayaka Itagaki;C. Yamamoto;K. Taguchi;Masayuki Yamamoto;Y. Kumagai;T. Kaji
中科院分区：
文献类型：
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作者：
Y. Shinkai;T. Kimura;Ayaka Itagaki;C. Yamamoto;K. Taguchi;Masayuki Yamamoto;Y. Kumagai;T. Kaji
镉是一种环境亲电体，可修饰蛋白质反应性硫醇，如Kelch样ECH相关蛋白1（Keap 1），核因子-红细胞2相关因子2（Nrf2）的负调节因子。在本研究中，我们研究了Keap1-Nrf2系统在血管内皮细胞对镉的细胞反应中的作用。暴露于镉的牛主动脉内皮细胞导致Keap1和Nrf2激活的修改，从而上调不仅其典型的下游蛋白，但也金属硫蛋白-1/2。用siRNA介导的Nrf2或Keap1敲低的实验支持Keap1-Nrf2系统参与金属硫蛋白-1/2表达的调节。此外，染色质免疫沉淀试验表明，Nrf2被招募到牛金属硫蛋白-2基因的启动子区的抗氧化反应元件在镉的存在下。这些结果表明，转录因子Nrf2起作用，至少部分，在金属硫蛋白表达的变化介导的暴露于镉的作用。
Cadmium is an environmental electrophile that modifies protein reactive thiols such as Kelch-like ECH-associated protein 1 (Keap1), a negative regulator of nuclear factor-erythroid 2-related factor 2 (Nrf2). In the present study, we investigated a role of the Keap1–Nrf2 system in cellular response to cadmium in vascular endothelial cells. Exposure of bovine aortic endothelial cells to cadmium resulted in modification of Keap1 and Nrf2 activation, thereby up-regulating not only its typical downstream proteins but also metallothionein-1/2. Experiments with siRNA-mediated knockdown of Nrf2 or Keap1 supported participation of the Keap1–Nrf2 system in the modulation of metallothionein-1/2 expression. Furthermore, chromatin immunoprecipitation assay showed that Nrf2 was recruited to the antioxidant response element of the promoter region of the bovine metallothionein-2 gene in the presence of cadmium. These results suggest that the transcription factor Nrf2 plays, at least in part, a role in the changes in metallothionein expression mediated by exposure to cadmium.