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Study of the cleavage of diphtheria taxin receptor by ADAM12

Research Project

Project/Area Number 15590407
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Bacteriology (including Mycology)
Research InstitutionUniversity of Occupational and Environmental Health, Japan

Principal Investigator

UMATA Toshiyuki  University of Occupational and Environmental Health, Japan Research Facility for Occupational and Environmental Health, Associate Professor, 産業医学研究支援施設, 助教授 (30213482)

Co-Investigator(Kenkyū-buntansha) OHTSUBO Motoaki  Hiroshima University, Rrsearch institute for Radiation Biology and Medicine, Research Associate, 原爆放射線医学研究所, 助手 (10211799)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsdiphtheria toxin receptor / lysophosphatidic acid / cleavage of extracelular domain / ADAM / NAC / ADAM12 / MAPKカスケード
Research Abstract

Lysophosphatidic acid (LPA) induces ectodomain shedding of diphtheria toxin receptor (DTR) in Vero cells. It has also been known that LPA generates reactive oxygen species (ROS). In the present study, to clarify whether ROS were implicated in LPA-induced DTR shedding, we investigated the effects of N-acetyl-L-cysteine (NAC), a ROS scavenger. NAC inhibited LPA-induced DTR shedding, but another ROS scavengers (ascorbic acid and a-tocopherol) did not. However, NAC, ascorbic acid and a-tocopherol suppressed ROS production in LPA-treated cells. Thus, NAC inhibited shedding in ROS independent manner. NAC only had a sulfhydryl group in three reagents, so, another reagents (L-cysteine, cysteamine) having sulfhydryl group were examined. These reagents also inhibited shedding. However, NAC treated with oxidizing agent did not inhibit shedding. These results suggest that the sulfhydryl group in NAC is important for shedding inhibition. ADAM has a cysteine-zinc bond that exists between the critical cysteine of the prodomain and the zinc atom of the active site. So, we examined whether NAC influenced to ADAM family. NAC also inhibited HB-EGF shedding induced by 4-aminophenylmercuric acetate (APMA) which activates latent metalloproteases by inducing autocatalytic cleavage and removal of the enzyme prodomain inhibitory region. Altogether, these results suggest that inhibitory effect of NAC on LPA-induced shedding might be related to inhibition of ADAM protease.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (16 results)

All 2004 2003 Other

All Journal Article (14 results) Publications (2 results)

  • [Journal Article] ヘパリン結合性上皮成長因子(EGF)様増殖因子の刺激誘導による活性化2004

    • Author(s)
      馬田 敏幸
    • Journal Title

      産業医科大学雑誌 26

      Pages: 85-97

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Mechanism for Activation of Heparin-Binding EGF-Like Growth Factor Induced by Stimuli.2004

    • Author(s)
      Toshiyuki Umata
    • Journal Title

      J UOEH 26(1)

      Pages: 85-97

    • NAID

      110001259602

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Activation of Heparin-Binding EGF-Like Growth Factor Induced by Stimuli.2004

    • Author(s)
      Toshiyuki Umata
    • Journal Title

      J Radiat Biol Res Commun 38

      Pages: 348-360

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] ヘパリン結合性上皮成長因子(EGF)様増殖因子の刺激誘導による活性化2004

    • Author(s)
      馬田 敏幸
    • Journal Title

      産業医科大学雑誌 26・3

      Pages: 85-97

    • Related Report
      2004 Annual Research Report
  • [Journal Article] ストレスによるヘパリン結合性EGF様増殖因子の活性化機構2003

    • Author(s)
      馬田 敏幸
    • Journal Title

      放射線生物研究 38

      Pages: 348-360

    • NAID

      40006070123

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] c-myc Induces Autophagy in Rat 3Y1 Fibroblast Cells2003

    • Author(s)
      Tsuneoka M.
    • Journal Title

      Cell Structure and Function 28

      Pages: 195-204

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The Stress- and Inflammatory Cytokine-induced Ectodomain Shedding of Heparin-binding Epidermal Growth Factor-like Growth Factor Is Mediated by p38 MAPK, Distinct from the 12-O-Tetradecanoylphorbol-13-acetate- and Lysophosohatidic Acid-induced Signaling Cascades2003

    • Author(s)
      Takenobu T.
    • Journal Title

      Journal of Biological Chemistry 278

      Pages: 17255-17262

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Inhibition of Proteasome-Dependent Degradation of Weel in G2-Arrested Hep3B Cells by TGFβ1.2003

    • Author(s)
      Hashimoto O.
    • Journal Title

      Molecular Carcinogenesis 36

      Pages: 171-182

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Troglitazone Induces p27kip1-Associated Cell-Cycle Arrest Through Down-regulating Skp2 in Human Hepatoma Cells2003

    • Author(s)
      Koga H.
    • Journal Title

      Hepatology 37

      Pages: 1086-1096

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] c-myc Induces Autophagy in Rat 3Y1 Fibroblast Cells.2003

    • Author(s)
      Makoto Tsuneoka
    • Journal Title

      Cell Struct and Function 28

      Pages: 195-204

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The Stress- and Inflammatory Cytokine-induced Ectodomain Shedding of Heparin-binding Epidermal Growth Factor-like Growth Factor Is Mediated by p38 MAPK, Distinct from the 12-O-Tetradecanoylphrbol-13-acetate- and Lysophosphatidic Acid-induced Signaling Cascades.2003

    • Author(s)
      Hisanori Takenobu
    • Journal Title

      J Biol Chem 278(19)

      Pages: 17255-17262

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Inhibition of Proteasome-Dependent Degradation of Wee1 In G2-Arrested Hep3B Cells by TGFβ1.2003

    • Author(s)
      Osamu Hashimoto
    • Journal Title

      Molecular Carcinogenesis 36

      Pages: 171-182

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Troglitazone Induces p27kip 1-Associated Cell-Cycle Arrest Trough Down-regulating Skp2 in Human Hepatoma Cells.2003

    • Author(s)
      Hironori Koga
    • Journal Title

      Hepatology 37

      Pages: 1086-1096

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Loss of p53 induces M-phase retardation following G2 DNA damage checkpoint abrogation.2003

    • Author(s)
      Yuzuru Minemoto
    • Journal Title

      Archives of Biochemistry and Biophysics 412

      Pages: 13-19

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Takenobu T.: "The Stress- and Inflammatory Cytokine-induced Ectodomain Shedding of Heparin binding Epidermal Growth Factor-like Growth Factor Is Mediated by p38 MAPK, Distinct from the 12-O-Tetradecanoylphorbol-13-acetate- and Lysophosohatidic Acid-induced Signaling Cascades"Journal of Biological Chemistry. 278. 17255-17262 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tsuneoka M.: "c-myc Induces Autophagy in Rat 3Y1 Fibroblast Cells"Cell Structure and Function. 28. 195-204 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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