Regulation of the expression of cystine transporter by oxidative stress.

氧化应激调节胱氨酸转运蛋白的表达。

• 批准号: 13680706
• 负责人: SATO Hideyo
• 金额: $ 2.3万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13680706/
• 关键词: cystine; amino acid transport; oxidative stress; glutathione; transcriptional regulation

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.

谷氨酸是抗氧化系统的必需分子之一。在哺乳动物细胞中，胱氨酸/谷氨酸交换转运体系统x_c^-对维持细胞内谷胱甘肽水平起着重要作用。本研究对由x_c^-系统组成的xCT表达的调控机制进行了研究，得到以下结果。(1)亲电试剂对xCT mRNA的诱导作用是通过位于小鼠xCT基因转录起始位点上游约150 bp处的亲电反应元件（EpRE）来调节的。这种诱导是由转录因子Nrf 2介导的。(2)胱氨酸缺乏对xCT mRNA的诱导通过位于EpRE下游的约30 bp的区域进行调节。(3)xCT mRNA在小鼠脑室周围器官和脑膜中强烈表达。(4)在非洲爪蟾卵母细胞和NIH 3 T3细胞中共表达xCT和rBAT以及共表达xCT和4F 2 hc可诱导x_c^-系统的活性。

项目成果

Sato. H.. Kuriyama-Matsumura, K., Hashimoto, T., Sasaki, H., Wang, H., Ishii, T.,Mann, G. and Bannai, S.: "Effect of oxygen on induction of the cystine transporter by bacterial lipopolysaccharide in mouse peritoneal macrophages"J. Biol. Chem.. 276. 10407-

佐藤。

Hiromi Sasaki: "Electrophile response element-mediated induction of the cystine/glutamate exchange transporter gene expression"The Journal of Biological Chemistry. 277・47. 44765-44771 (2002)

佐佐木弘美：“电反应元件介导的胱氨酸/谷氨酸交换转运蛋白基因表达的诱导”生物化学杂志277·47（2002）。

Hideyo Sato, et al.: "Distribution of cystine/glutamate exchange transporter, system x^-_c, in the mouse brain"The Journal of Neuroscience. 22・18. 8028-8033 (2002)

Hideyo Sato 等人：“小鼠大脑中胱氨酸/谷氨酸交换转运蛋白系统 x^-_c 的分布”《神经科学杂志》22・18（2002 年）。

Suzuka Okuno: "Role of cystine transport in intracellular glutathione level and cisplatin resistance in human ovarian cancer cell"British Journal of Cancer. 88. 951-956 (2003)

Suzuka Okuno：“胱氨酸转运对人卵巢癌细胞内谷胱甘肽水平和顺铂耐药性的作用”英国癌症杂志。

Sasaki, H., Sato, H., Kuriyama-Matsumura, K., Sato, K., Maebara, K., Wang, H., Tamba, M., Itoh, K., Yamamoto, M. and Bannai, S.: "Electrophile response element-mediated induction of the cystine/glutamate exchange transporter gene expression"J. Biol. Chem.

Sasaki, H.、Sato, H.、Kuriyama-Matsumura, K.、Sato, K.、Maebara, K.、Wang, H.、Tamba, M.、Itoh, K.、Yamamoto, M. 和 Bannai, S