2002 Fiscal Year Final Research Report Summary
Regulation of the expression of cystine transporter by oxidative stress.
| Project/Area Number |
13680706
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional biochemistry
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| Research Institution | University of Tsukuba |
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Principal Investigator |
SATO Hideyo Institute of Basic Medical Sciences, Assistant Professor, 基礎医学系, 講師 (60235380)
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| Project Period (FY) |
2001 – 2002
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| Keywords | cystine / amino acid transport / oxidative stress / glutathione / transcriptional regulation |
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| Research Abstract |
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.
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[Publications] Ruiz,E., Siow, R. C. M., Bartlett, S. R., Jenner, A. M., Sato. H., Bannai, S.and Mann, G.E.: "Vitamin C inhibits diethylmaleate-induced L-cystine transport in human vascular smooth muscle cells"Free Rad. Biol. Med.. 34. 103-110 (2003)
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「研究成果報告書概要(欧文)」より
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[Publications] Okuno, S., Sato. H.. Kuriyama-Matsumura, K., Wang, H., Tamba, M., Sohda, S., Hamada, H., Yoshikawa, H., Kondo, T. and Bannai, S.: "Role of cystine transport in intracellular glutathione level and cisplatin resistance in human ovarian cancer cell"Br. J. Cancer. 88. 951-956 (2003)
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[Publications] Sato. H.. Tamba, M., Okuno, S., Sato, K., Keino-Masu, K., Masu, M. and Bannai, S.: "Distribution of cystine/glutamate exchange transporter, System x_c^-, in the mouse brain"J. Neurosci.. 22. 8028-8033 (2002)
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[Publications] 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.. 277. 44765-44771 (2002)
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[Publications] 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. 10407-10412 (2001)
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