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Establishment of screening systems that detect chemicals against circulatory diseases using redox changes as an indicator.

Research Project

Project/Area Number 07557374
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Biological pharmacy
Research InstitutionSHOWA UNIVERSITY

Principal Investigator

NOSE Kiyoshi  (Showa Univ.Sch.Pharm.Sci., Professor), 薬学部, 教授 (70012747)

Co-Investigator(Kenkyū-buntansha) MATSUMURA Toshiharu  (Meiji Institute of Health, Vice president), 副所長
YAMAMOTO Toshinori  (Showa Univ.Sch.Pharm.Sci., Professor), 薬学部, 教授 (30112741)
MASHIMO Jun'ichi  (Showa Univ.Sch.Pharm.Sci., Research Associate), 薬学部, 助手 (60054045)
EGAWA Kiyoshi  (Showa Univ.Sch.Pharm.Sci., Lecturer), 薬学部, 講師 (00095879)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1997: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1996: ¥3,300,000 (Direct Cost: ¥3,300,000)
KeywordsWAFl / p21 / drug screening systems / luciferase / Spl transcription factor / anti-cancer drugs / p53蛋白質 / レドクス / 遺伝子発現 / WAF-1
Research Abstract

The WAF1/p21 is one of target genes of tumor suppressor p53 that is regulated through redox-based mechanisms. Assay systems were constructed using WAF1/p21 gene enhancer and luciferase as reporters. DNA fragments of human p21 gene 5'-upstream -2400 bp and -210 bp were ligated to the luciferase gene, and plasmids were introduced into p53-deficient Saos-2 or p53-mutated TMK-l cells. Stable lines that express luciferase in response to activator of p21 gene (butyrate) established and used for the screening. Among 1300 culture broths of Streptomyces, three active substances were detected and identified as Actinomycin D analogue, phleomycin and trichostatin A.These substances induced p21 gene expression in p53-independent manner, and transcriptional elements for the induction were revealed to be the Spl elements that localize -150 bp from the cap sites. Further screening will detect novel substances that are useful as anti-tumorigenic or anti-fungal drugs.

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Shibanuma, M. & Nose, K.: "Forced expression of hic-5 enhanced differentiation phenotypes" Int. J. Biochem. Cell Biol.(印刷中). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Shibanuma, M. et al.: "Induction of senescence-like phenotypes by the forced expression" Mol. Cell. Biol.17. 1224-1235 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Arata, S., et al.: "Inhibition of colony formation of NIH3T3 cells by H3p27" J. Cell. Physiol.170. 19-26 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mashimo, J. et al.: "Decrease in the expression of a novel TGEβ1-inclucible" Cancer Lett.113. 213-219 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ohba, M. & Nose, K.: "Functional activation of the egr-1 gene by hydrogen peroxide" Biochem. J.316. 381-383 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Shibanuma, M.& Nose, k.: "Forced expression of hic-5 enhances differentiation phenotypes of RCT-l cells" lnt.J.Biochem.cell Biol.(in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Shibanuma, M., et al.: "lnduction of senescence-like phenotypes by the forced expression of hic-5" Mol.Cell Biol.17. 1224-1235 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Arata, S., et al.: "lnhibition of colony formation of NIH3T3 cells by HSP27" J.Cell Physiol.170. 19-26 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mashimo, J., et al.: "Decrease in the expression of a novel TGFbeta1-inducible TSC-36 gene" Cancer Lett.113. 213-219 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ohba, M.& Nose, K.: "Functional activation of the efr-l gene by hydrogen peroxide" Biochem.J.316. 381-383 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Shibanuma,M. & Nose,K.: "Forced expression of hic-5 enhamus differentiation phinotypes of RCT-1 cells." Int.J.Biochem,Cell Biol.(印刷中). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Shibanuma,M. et al.: "Induction of senescence-like phenotypes by the forced expression of hic-5" Mol.Cell.Biol.17. 1224-1235 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Arata,S.et al.: "Inhibition of colony formation of NIH3T3 cells by HSP27" J.Cell.Physiol.170. 19-26 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Mashimo,J.,et al.: "Decrease in the expression of a novel TGFB1-inducible TSC-36 gene" Caucer Lett.113. 213-219 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ohba,M. & Nose,K.: "Functional activation of the egr-1 gene by hydrogen peroxide" Biochem.J.316. 381-383 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] M.Shibanuma et al.: "Induction of senescence-like phenotypes by the forced expression of hic-5" Mol.Cell.Biol.(印刷中). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] J.Mashimo et al.: "Decrease in the expression of a novel TGFBi-inducible gane" Cancer Lett.(印刷中). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] S.Arata: "Inhivition of colony formation of NIH3T3 Cells" J.Cell.Physiol. 170. 19-26 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 荒田 悟: "Effect of the overexpression of the small heat shock protein, HSP27, on the sensitivity of human fibroblast cells exposed to oxidative stress" J. Cell. Physil.163. 458-465 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 柴沼 質子: "Activation of DNA synthesis and expression of the JE gene by catalase in mouse in osteoblastic cells.: Possible involvement of hydrogen peroxide in negative growth reguration." Exp. Cell. Res.218. 132-136 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 江川 清: "Isolation of a novel ras-recision gene that is induced by hydrogen peroxide from a mause osteoblastic line, MC3T3." FEBS Lett.372. 74-77 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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