Regulation of the expression of cystine transporter by oxidative stress.

谷胱甘肽是抗氧化系统的重要分子之一。在哺乳动物细胞中，半胱氨酸/谷氨酸交换转运蛋白系统x_c^-在维持细胞内谷胱甘肽水平方面起着重要作用。本研究对XCT基因的表达调控机制进行了研究，获得了以下结果。(1)亲电试剂对小鼠XCT基因转录起始点上游约150个碱基的电泳性反应元件(EpRE)调控XCT基因的表达。这种诱导是由转录因子Nrf2介导的。(2)半胱氨酸缺乏对XCT mRNA的诱导是通过EpRE下游约30bp的区域进行调控的。(3)小鼠脑内XCT基因在脑室周器官和脑膜中有较强的表达。(4)在非洲爪哇卵母细胞和NIH3T3细胞中，共表达XCT和rBAT以及共表达XCT和4F2hc均可诱导x_c^-系统的活性。

Glutathione is one of the essential molecules for the antioxidant system. In mammalian cells, the cystine/glutamate exchange transporter designated system x_c^- plays an important role for maintaining the intracellular glutathione level. In this study, the regulatory mechanism of the expression of xCT consisting of system x_c^- was investigated and the following results were obtained. (1) The induction of xCT mRNA by electrophilic reagents was regulated via electrophile response element (EpRE) located on approximately 150 bp upstream of the transcription initiation site of mouse xCT gene. This induction was mediated by a transcription factor, Nrf2. (2) The induction of xCT mRNA by cystine deficiency was regulated via the region consisting of approximately 30 bp located on the downstream of EpRE. (3) The xCT mRNA was strongly expressed in circumventricular organ and meninges in the mouse brain. (4) The activity of system x_c^- was induced by co-expressing xCT and rBAT as well as by co-expressing xCT and 4F2hc in Xenopus oocytes and NIH3T3 cells.