Takenaka Yasuhiro, Haga Nobuyuki, Inoue Ikuo, Nakano Takanari, Ikeda Masaaki, Katayama Shigehiro, Awata Takuya
Department of Diabetes and Endocrinology, Saitama Medical University, Saitama, Japan
Department of Biotechnology, Ishinomaki Senshu University, Ishinomaki, Miyagi, Japan.
Eukaryot Cell. 2014 Sep;13(9):1181-90. doi: 10.1128/EC.00112-14. Epub 2014 Jul 7.
Here, we describe the isolation of two nickel-induced genes in Paramecium caudatum, NCI16 and PcGST1, by subtractive hybridization. NCI16 encoded a predicted four-transmembrane domain protein (∼16 kDa) of unknown function, and PcGST1 encoded glutathione S-transferase (GST; ∼25 kDa) with GST and glutathione peroxidase (GPx) activities. Exposing cells to cobalt chloride also caused the moderate upregulation of NCI16 and PcGST1 mRNAs. Both nickel sulfate and cobalt chloride dose dependently induced NCI16 and PcGST1 mRNAs, but with different profiles. Nickel treatment caused a continuous increase in PcGST1 and NCI16 mRNA levels for up to 3 and 6 days, respectively, and a notable increase in H₂O₂ concentrations in P. caudatum. NCI16 expression was significantly enhanced by incubating cells with H₂O₂, implying that NCI16 induction in the presence of nickel ions is caused by reactive oxygen species (ROS). On the other hand, PcGST1 was highly induced by the antioxidant tert-butylhydroquinone (tBHQ) but not by H2O2, suggesting that different mechanisms mediate the induction of NCI16 and PcGST1. We introduced a luciferase reporter vector with an ∼0.42-kb putative PcGST1 promoter into cells and then exposed the transformants to nickel sulfate. This resulted in significant luciferase upregulation, indicating that the putative PcGST1 promoter contains a nickel-responsive element. Our nickel-inducible system also may be applicable to the efficient expression of proteins that are toxic to host cells or require temporal control.
在此,我们描述了通过消减杂交法在尾草履虫中分离出两个镍诱导基因,即NCI16和PcGST1。NCI16编码一种预测的具有四个跨膜结构域的未知功能蛋白(约16 kDa),而PcGST1编码具有谷胱甘肽S - 转移酶(GST;约25 kDa)活性以及谷胱甘肽过氧化物酶(GPx)活性的蛋白。将细胞暴露于氯化钴也会导致NCI16和PcGST1 mRNA适度上调。硫酸镍和氯化钴均呈剂量依赖性地诱导NCI16和PcGST1 mRNA,但诱导模式不同。镍处理分别使PcGST1和NCI16 mRNA水平持续增加长达3天和6天,并且尾草履虫中的H₂O₂浓度显著升高。用H₂O₂孵育细胞可显著增强NCI16的表达,这意味着在镍离子存在下NCI16的诱导是由活性氧(ROS)引起的。另一方面,抗氧化剂叔丁基对苯二酚(tBHQ)可高度诱导PcGST1,但H₂O₂不能,这表明介导NCI16和PcGST1诱导的机制不同。我们将一个带有约0.42 kb假定的PcGST1启动子的荧光素酶报告载体导入细胞,然后将转化体暴露于硫酸镍中。这导致荧光素酶显著上调,表明假定的PcGST1启动子含有一个镍反应元件。我们的镍诱导系统也可能适用于对宿主细胞有毒或需要时间控制的蛋白质的高效表达。