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Expression and patho-physiological function of cystine transporter

Research Project

Project/Area Number 13470031
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionUniversity of Tsukuba

Principal Investigator

BANNAI Shiro  University of Tsukuba, Institute of Basic Medical Sciences, Professor, 基礎医学系, 教授 (70019579)

Co-Investigator(Kenkyū-buntansha) SATO Hideyo  Yamagata University, Faculty of Agriculture, Associate Professor, 農学部, 助教授 (60235380)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2003: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2002: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2001: ¥6,200,000 (Direct Cost: ¥6,200,000)
Keywordscystine / glutathione / amino acids / transporter / redox / oxidative stress / gene expression / 酸素 / 遺伝子発現調節 / システイン / 活性酸素
Research Abstract

Transport system x_c^-mediates the exchange transport between extracellular cystine and intracellular glutamate. This system is composed of two proteins, xCT and 4F2hc, and the former is thought to be the actual transporter. In this project we have investigated the expression and the transcriptional regulation of xCT gene in some cells and tissues and have tried to produce xCT gene-knockout mouse to elucidate the patho-physiological role of system x_c^-in whole mouse. The results are as follows
1.xCT gene was strongly expressed in meninges and some circumventricular organs, e. g., area postrema and subfornical organ. This may suggest that system x~' contributes to the maintenance of the redox state (i, e., cysteine/cystine ratio) in the cerebrospinal fluid
2.System x_c^-was highly expressed in cisplatin-resistant variant of human ovarian cancer cell lines compared with cisplatin sensitive cell lines. It was found that system x_c^-contributes to the cisplatin-resistancy by increasing glutathione level
3.We have studied the mechanism by which system x_c^-activity is induced by electrophilic agents. We found that several electrophile response elements exist in the 5'-flanking region of xCT gene and that electrophilic agents induce the xCT transciptionally via one of these elements in association with the transcription factor Nrf2
4.We have studied the mechanism by which system x_c^-is induced by cystine deprivation. We found that two amino acid response elements exist in the S'-flanking region of xCT gene and that the xCT is induced transcriptionally by cystine deprivation via these two elements in association with the transcription factor ATF4
5.xCT gene-knockout mice have been successfully produced. At present these mice, three months after birth, are apparently normal and the phenotype analysis remains to be investigated

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Hideyo Sato: "Effect of oxygen on induction of the cystine transporter by bacterial LPS in mouse peritoneal macrophages."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
      2003 Final Research Report Summary
  • [Publications] Hideyo Sato: "Distribution, of cystine/glutamate exchange transporter, system x_c^-, in the mouse brain."Journal of Neuroscience. 22・18. 8028-8033 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hiromi Sasaki: "Electrophile response element-mediated induction of the cystine/glutamate exchange transporter gene expression."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
      2003 Final Research Report Summary
  • [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
      2003 Final Research Report Summary
  • [Publications] Hongyu Wang: "Expression of the activity of cystine/glutamate exchange transporter, system, x_c^-, by xCT and rBAT."Biochemical and Biophysical Research Communications. 305. 611-618 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suzuka Okuno: "Role of cystine transport in intracellular glutathione level and cisplatin resistance in human ovarian cancer cell lines."British Journal of Cancer. 88. 951-956 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hideyo Sato, et al.: "Effect of oxygen on induction of the cystine transporter by bacterial LPS in mouse peritoneal macrophages"Journal of Biological Chemistry. 276(13). 10407-10412 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hideyo Sato, et al.: "Distribution of cystine/glutamate exchange transporter, system x_c^-, in the mouse brain"Journal of Neuroscience. 22(18). 8028-8033 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hiromi Sasaki, et al.: "Electrophile response element-mediated induction of the cystine/glutamate exchange transporter gene expression"Journal of Biological Chemistry. 277(47). 44765-44771 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hongyu Wang, et al.: "Expression of the activity of cystine/glutamate exchange transporter, system x_c^-, by xCT and rBAT"Biochemical and Biophysical Research Communications. 305. 611-618 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suzuka Okuno, et al.: "Role of cystine transport in intracellular glutathione level and cisplatin resistance in human ovarian cancer cell lines"British Journal of Cancer. 88. 951-956 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hideyo Sato: "Effect of oxygen on induction of the cystine transporter by bacterial LPS in mouse peritoneal macrophages"Journal of Biological Chemistry. 276・13. 10407-10412 (2001)

    • Related Report
      2003 Annual Research Report
  • [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)

    • Related Report
      2003 Annual Research Report
  • [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)

    • Related Report
      2003 Annual Research Report
  • [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)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hongyu Wang: "Expression of the activity of cystine/glutamate exchange transporter, system x_c^-, by xCT and rBAT"Biochemical and Biophysical Research Communications. 305. 611-618 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Suzuka Okuno: "Role of cystine transport in intracellular glutathione level and cisplatin resistance in human ovarian cancer cell lines"British Journal of Cancer. 88. 951-956 (2003)

    • Related Report
      2003 Annual Research Report
  • [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)

    • Related Report
      2002 Annual Research Report
  • [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)

    • Related Report
      2002 Annual Research Report
  • [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)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hideyo Sato: "Effect of oxygen on induction of the cystine transporter by bacterial LPS in mouse peritoneal macrophages"Journal of Biological Chemistry. 276. 10407-10412 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kazumi Kuriyama-Matsumura: "Effects of hyperoxia and iron regulatory protein-1 activity and the ferritin synthesis in mouse macrophages"Biochimica et Biophysica Acta. 1544. 370-377 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kayoko Sasaki: "Restored vulnerability of cultured endothelial cells to high glucose by iron replenishment"Biochemical and Biophysical Research Communications. 289. 664-669 (2001)

    • Related Report
      2001 Annual Research Report

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

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