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Regulation of the expression of cystine transporter by oxidative stress.

Research Project

Project/Area Number 13680706
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionUniversity of Tsukuba

Principal Investigator

SATO Hideyo  Institute of Basic Medical Sciences, Assistant Professor, 基礎医学系, 講師 (60235380)

Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordscystine / amino acid transport / oxidative stress / glutathione / transcriptional regulation
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.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Emilio Ruiz: "Vitamin C inhibits diethylmaleate-induced L-cystine transport in human vascular smooth muscle cells"Free Radical Biology & Medicine. 34・1. 103-110 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hideyo Sato: "Distribution of cystine/glutamate exchange transporter, system x_c^-, in the mouse brain"The Journal of Neuroscience. 22・18. 8028-8033 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hideyo Sato: "Effect of oxygen on induction of the cystine transporter by bacterial lipopolysaccharide in mouse peritoneal macrophages"The Journal of Biological Chemistry. 276・13. 10407-10412 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kazumi Kuriyama-Matsumura: "Effects of hyperoxia and iron on iron regulatory protein-1 activity and the ferritin synthesis in mouse peritoneal macrophages"Biochimica et Biophysica Acta. 1544. 370-377 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kuriyama-Matsumura, K., Sato. H., Suzuki, M. and Baunai, S.: "Effects of hyperoxia and iron on iron regulatory protein-1 activity and the ferritin synthesis in mouse peritoneal macrophages"Biochim. Biophys. Acta. 1544. 370-377 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Emilio Ruiz, et al.: "Vitamin C inhibits diethylmaleate-induced L-cystine transport in human vascular smooth muscle cells"Free Radical Biology & Medicine. 34・1. 103-110 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hiromi Sasaki, et al.: "Electrophile response element-mediated induction of the cystine/glutamate exchange transporter gene expression"The Journal of Biological Chemistry. 277・47. 44765-44771 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 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)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sato, H., et al.: "Effecto of oxygen on induction of the cystine transporter by bacterial pipopolysaccharide in mouse peritoneal macrophages"J. Biol. Chem.. 276(13). 10407-10412 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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