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Analysis of the mechanism and biological function of the internalization of thioredoxin into cells via lipid raft.

Research Project

Project/Area Number 17590247
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General medical chemistry
Research InstitutionKyoto University

Principal Investigator

YODOI Junji (2006)  Institute for Virus Research Kyoto University, Professor, ウイルス研究所, 教授 (80108993)

近藤 則彦 (2005)  京都大学, ウイルス研究所, 助手 (50378949)

Co-Investigator(Kenkyū-buntansha) MASUTANI Hiroshi  Institute for Virus Research Kyoto University, Associate Professor, ウイルス研究所, 助教授 (50252523)
淀井 淳司  京都大学, ウイルス研究所, 教授 (80108993)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsthioredoxin / redox regulation / lipid rafts / modified protein / ストレスシグナル / レドックス(酸化還元)
Research Abstract

Thioredoxi-1 (TRX) plays important roles on cellular signaling by controlling the redox state of cysteines residues in target proteins. TRX is released in response to oxidative stress and shows various biological functions also in extracellular environment. We have reported the mechanism of the internalization of TRX into cells.
Last year, Dr. Kondo revealed that TRX (TRX-C35), which the cysteine at residue 35 of active site of TRX was replaced with serine, binds rapidly to cell surface and is internalized into cells through lipid rafts in the plasma membrane. Since the internalization of TRX-C35 into cells was observed especially in virus-infected T cells or activated T cells, lipid rafts is considered to play important roles in TRX-C35 entry into cells. Meanwhile, TRX-C35 is a useful material to analyze TRX binding to cell surface or TRX uptake into cells.
This year, we examined the biological function of TRX-C35.
We examined an stress-induced apoptosis of Jurkat T cells triggered by anti-cancer agent cis-diammininedichloroplatinum (CDDP). The results show that the internalized TRX-C35 bound to endogenous TRX, resulting in the generation of intracellular reactive oxygen species (ROS) and enhanced CDDP-induced apoptosis via a ROS-mediated pathway involving apoptosis signal-regulating kinase-1 (ASK-1) activation.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (33 results)

All 2006 2005 Other

All Journal Article (33 results)

  • [Journal Article] Thioredoxin inhibits NMDA-induced neurotoxicity in the rat retia.2006

    • Author(s)
      Inomata Y
    • Journal Title

      J Neurochem 98

      Pages: 372-385

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Human thioredoxin-1 ameliorates experimentalmurine colitis I association with suppressed macrophage inhibitory factor production.2006

    • Author(s)
      Tamaki H
    • Journal Title

      Gastroenterology 131

      Pages: 1110-1121

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Thioredoxin protects against joint destruction in a murine arthritis model.2006

    • Author(s)
      Tsuii G
    • Journal Title

      Free Radic Biol Med 40

      Pages: 1721-1731

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Recombinant human thioredoxin ameliorates lipoplysaccharide-induced bronchoalveolar neutrophil infiltration in rat.2006

    • Author(s)
      Ueda S
    • Journal Title

      Life Sci 79

      Pages: 1170-1177

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Redox regulation of human thioredoxin netwaork.2006

    • Author(s)
      Kondo N
    • Journal Title

      Antioxid Redox Signal 8

      Pages: 1881-1890

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] チオレドキシンによるレドックスとストレスシグナル制御2006

    • Author(s)
      増谷 弘
    • Journal Title

      特集 活性酸素・フリーラジカル機能と病態解明への新たな展開 : バイオスピンとシグナル伝達 細胞工学 25

      Pages: 143-148

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Thioredoxin inhibits NMDA-induced neurotoxicity in the rat retia.2006

    • Author(s)
      Inomata Y, et al.
    • Journal Title

      J Neurochem 99

      Pages: 372-385

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Human thioredoxin-1 ameliorates experimentalmurine colitis I association with suppressed macrophage inhibitory factor production.2006

    • Author(s)
      Tamaki H, et al.
    • Journal Title

      Gastroenterology 131

      Pages: 1110-1121

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Thioredoxin protects against joint destruction in a murine arthritis model.2006

    • Author(s)
      Tsuji G, et al.
    • Journal Title

      Free Radic Biol Med 40

      Pages: 1721-1731

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Recombinant human thioredoxin ameliorates lipoplysaccharide-induced bronchoalveolar neutrophil infiltration in rat.2006

    • Author(s)
      Ueda S, et al.
    • Journal Title

      Life Sci 79

      Pages: 1170-1177

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Redox regulation of human thioredoxin netwaork.2006

    • Author(s)
      Kondo N, et al.
    • Journal Title

      Antioxid Redox Signal 8

      Pages: 1881-1890

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Thioredoxin inhibits NMDA-induced neurotoxicity in the rat retia.2006

    • Author(s)
      Inomata Y, Nakamura H, Tanito M, Teratani A, Kawaji T, Kondo N, Yodoi J, Tanihara H
    • Journal Title

      J Neurochem 98

      Pages: 372-385

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Human thioredoxin-1 ameliorates experimentalmurine colitis I association with suppressed macrophage2006

    • Author(s)
      Tamaki H, Nakamura H, Nishio A, Nakase H, Ueno S, Uza N, Kido M, Inoue S, Asada M, Kiriya K, Kitamura H, Ohashi S, Fukui T, Kawasaki K, Matsuura M, Ishii Y, Okazaki K, Yodoi J, Chiba T
    • Journal Title

      Gastroenterology 131

      Pages: 1110-1121

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Thioredoxin protects against joint destruction in a murine arthritis model.2006

    • Author(s)
      Tsuji G, Koshiba M, Nakamura H, Kosaka H, Hatachi S, Kurimoto C, Kurosaka M, Hayashi Y, Yodoi J, Kumagai S
    • Journal Title

      Free Radic Biol Med 40

      Pages: 1721-1731

    • NAID

      120002055777

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Recombinant human thioredoxin ameliorates lipoplysaccharide-induced bronchoalveolar neutrophil2006

    • Author(s)
      Ueda S, Nakamura T, Yamada A, Teratani A, Matsui N, Furukawa S, Hoshino Y, Narita M, Yodoi J, Nakamura H
    • Journal Title

      Life Sci 79

      Pages: 1170-1177

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Redox regulation of human thioredoxin netwaork.2006

    • Author(s)
      Kondo N, Nakamura H, Masutani H, Yodoi J
    • Journal Title

      Antioxid Redox Signal 8

      Pages: 1881-1890

    • Related Report
      2006 Annual Research Report
  • [Journal Article] チオレドキシンによるレドックスとストレスシグナル制御2006

    • Author(s)
      増谷 弘, 淀井淳司
    • Journal Title

      特集 活性酸素・フリーラジカル機能と病態解明への新たな展開 : バイオスピンとシグナル伝達 細胞工学 25

      Pages: 143-148

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Redox regulation of mast cell histamine release in thioredoxin-1(TRX) transgenic mice.2006

    • Author(s)
      Son A, Nakamura H, Kondo N, Matsuo Y, Liu W, Oka S, Ishii Y, Yodoi J.
    • Journal Title

      Cell Research 16(2)

      Pages: 230-239

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Thioredoxin-1 suppresses lung injury and apoptosis induced by diesel exhaust particles (DEP) by scavenging reactive oxygen species and by inhibiting DEP-induced downregulation of Akt.2005

    • Author(s)
      Ahsan MK
    • Journal Title

      Free Radic Biol Med 39(12)

      Pages: 1549-1559

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Helicobacter felis-induced gastritis was suppressed in mice overexpressing thioredoxin-1.2005

    • Author(s)
      Kawasaki K
    • Journal Title

      Lab Invest 85(9)

      Pages: 1104-1117

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Redox regulation of lung inflammation by thioredoxin.2005

    • Author(s)
      Nakamura T
    • Journal Title

      Antioxid Redox Signal 7(1-2)

      Pages: 60-71

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cytoprotective effects of geranylgeranyllacetone against retinal photooxidative damage.2005

    • Author(s)
      Tanito M
    • Journal Title

      J Neurosci 25(9)

      Pages: 2396-2404

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] チオレドキシンと酸化ストレス応答2005

    • Author(s)
      淀井淳司
    • Journal Title

      酸化ストレスと肝疾患 第1輯

      Pages: 53-57

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] チオレドキシンシステム-蛋白質の酸化/還元に基づく機能制御2005

    • Author(s)
      松尾禎之
    • Journal Title

      別冊 医学のあゆみ レドックス-ストレス防御の医学

      Pages: 9-13

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Thioredoxin-1 suppresses lung injury and apoptosis induced by diesel exhaust particles (DEP) by scavenging reactive oxygen species and by inhibiting DEP-induced downregulation of Akt.2005

    • Author(s)
      Ahsan MK, et al.
    • Journal Title

      Free Radic Biol Med 39 (12)

      Pages: 1549-1559

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Helicobacter felis-induced gastritis was suppressed in mice overexpressing thioredoxin-1.2005

    • Author(s)
      Kawasaki K, et al.
    • Journal Title

      Lab Invest 85 (9)

      Pages: 1104-1117

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Redox regulation of lung inflammation by thioredoxin.2005

    • Author(s)
      Nakamura T, et al.
    • Journal Title

      Antioxid Redox Signal 7 (1-2)

      Pages: 60-71

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cytoprotective effects of geranylgeranyllacetone against retinal photooxidative damage.2005

    • Author(s)
      Tanito M, et al.
    • Journal Title

      J Neurosci 25 (9)

      Pages: 2396-2404

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cytoprotective effects of geranylgeranylacetone against retinal photooxidative damage.2005

    • Author(s)
      Tanito M, Kwon YW, Kondo N, Bai J, Masutani H, Nakamura H, Fujii J, Ohira A, Yodoi J.
    • Journal Title

      Journal of Neuroscience 25(9)

      Pages: 2398-2404

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Lipid-raft-mediated uptake of cysteine-modified thioredoxin-1 enhances cisplatin-induced apoptosis by inhibiting the endogenous thioredoxin-1.

    • Author(s)
      Kondo N
    • Journal Title

      Antioxid Redox Signal (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cell surface thioredoxin-1 : Possible involvement in thiol-mediated leukocyte-endthelial cell interaction through lipid rafts.

    • Author(s)
      Hara T
    • Journal Title

      Antioxid Redox Signal (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Lipid-raft-mediated uptake of cysteine-modified thioredoxin-1 enhances cisplatin-induced apoptosis by inhibiting the endogenous thioredoxin-1.

    • Author(s)
      Kondo N, et al.
    • Journal Title

      Antioxid Redox signal (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cell surface thioredoxin-1 : Possible involvement in thiol-mediated leukocyte-endthelial cell interaction through lipid rafts.

    • Author(s)
      Hara T, et al.
    • Journal Title

      Antioxid Redox Signal (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary

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Published: 2005-04-01   Modified: 2016-04-21  

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