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Studies on the specific pathway of energy metabolism held in tumor cells and their application on the development of anti-tumor drugs

Research Project

Project/Area Number 07557164
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section試験
Research Field 医薬分子機能学
Research InstitutionThe University of Tokushima

Principal Investigator

TERADA Hiroshi  Fac.Pharm.Sci., The University of Tokushima Professor, 薬学部, 教授 (00035544)

Co-Investigator(Kenkyū-buntansha) HORI Hitoshi  Fac.Engg., The University of Tokushima Professor, 工学部, 教授 (90119008)
SHINOHARA Yasuo  Fac.Pharm.Sci., The University of Tokushima Associate Professor, 薬学部, 助教授 (60226157)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥15,100,000 (Direct Cost: ¥15,100,000)
Fiscal Year 1996: ¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 1995: ¥9,300,000 (Direct Cost: ¥9,300,000)
Keywordshexokinase / tumor cells / anti-tumor drugs / energy metabolism / mitochondri / ミトコンドリア / 解糖系 / 阻害剤
Research Abstract

Previously, we found that type II hexokinase is predominantly expressed in malignant tumor cells synchronized with the expression of type 1 glucose transporter and concluded the possible formation of atypical pathway of energy metabolism in tumor cells. In this research project, we focused on this atypical pathway of energy metabolism, we tried to characterize it and to develop new anti-tumor drugs. The obtained findings are follows :
1) we isolated and characterized the promoter region of the gene encoding type II hexokinase (ref.1)
2) we examined the effects of various culture couditions on the steady state transcript level of type II hexokinase and found a possible regulation of the transcript level of this enzyme by oxygen concentration (not yet published)
3) to clarify the structural and functional features of this enzyme, we developed several chimera proteins between type II and type IV enzymes, and characterized their fouctional features (ref.4)
4) to know the functional features of mitochondria-bound hexokinase, we isolated tumor mitochondria and examined the preference of the membrane bound hexokinase for ATP molecules synthesized by various systems. As a result, mitochondria-bound hexokinase was found to use preferentially the ATP synthesized by oxidative phosphorylation (ref.4)

Report

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

    (28 results)

All Other

All Publications (28 results)

  • [Publications] J.Ichihara et al.: "Nucleotide Sequence of the 5'-Flanking Region of the Rat Type II Hexokinase" Biochim.Biophys.Acta. 1260. 365-368 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] E.Majima et al.: "Stabilities of the Fluorescent SH-Reagent Eosin-5-maleimide and Its Adducts with Sulfhydryl Compounds" Biochim.Biophys.Acta. 1243. 336-342 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] E.Majima et al.: "Translocation of Loops Regulates Transport Activity of Mitochondrial ADP/ATP Carrier Deduced from Formation of a Specific Intermolecular Disulfide Bridge Catalyzed by Copper-o-Phenanthroline" J.Biol.Chem.270. 29548-29554 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Kogure et al.: "Alteration of Enzyme Function of the Type II Hexokinase C-terminal Half on Replacement of Restricted Regions by Corresponding Regions of Glucokinase" J.Biol.Chem.271. 15230-15236 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Shinohara et al.: "Source of ATP for hexokinase-catalyzed glucose phosphorylation in tumor cells : dependence on the rate of oxidative phosphorylation relative to that of extramitochondrial ATP generation" Biochim.Biophys.Acta. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 篠原康雄、寺田 弘: "グルコキナーゼ遺伝子の重複融合による高等動物のヘキソキナーゼ遺伝子形成" 生化学. 67. 137-141 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 山崎尚志、篠原康雄、寺田 弘: "ミトコンドリアの輸送タンパク質のスーパーファミリー" 生体の科学. 46. 605-607 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Terada et al.: "Structural Requirements of Leukotriene Antagonists QSAR and Drug Design-New Developments and Application (T.Fujita.Ed.)" Elsevier, Amsterdam (1995). 341-367 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] J.Ichihara et al.: "Nucleotide Sequence of the 5'-Flanking Region of the Rat Type II Hexokinase Gene" Biochim.Biophys.Acta. 1260. 365-368 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] E.Majima et al.: "Stabilities of the Fluorescent SH-Reagent Eosin-5-maleimide and Its Adducts with Sulfhydryl Compounds" Biochim.Biophys.Acta. 1243. 336-342 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] E.Majima et al.: "Translocation of Loops Regulates Transport Activity of Mitochondrial ADP/ATP Carrier Deduced from Formation of a Specific Intermolecular Disulfide Bridge Catalyzed by Copper-o-Phenanthroline" J.Biol.Chem. 270. 29548-29554 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] K.Kogure et al.: "Alteration of Enzyme Function of the Type II Hexokinase C-terminal Half on Replacement of Restricted Regions by Corresponding Regions of Glucokinase" J.Biol.Chem. 271. 15230-15236 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Shinohara et al.: "Source of ATP for hexokinase-catalyzed glucose phosphorylation in tumor cells : dependence on the rate of oxidative phosphorylation relative to that of extramitochondrial ATP generation" Biochim.Biophys.Acta. (in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.Shinohara, H.Terada: "Evolution of the mammalian hexokinase gene by duplication and fusion of the glucokinase gene" Seikagaku. 67. 137-141 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] N.Yamazaki, Y.Shinohara.H.Terada: "Mitochondrial solute carrier superfamily" Seitainokagaku. 46. 605-607 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] H.Terada et al.: "Structural Requirements of Leukotriene Antagonists QSAR and Drug Design-New Developments and Applications (T.Fujita.Ed.)" Elsevier, Amsterdam. 341-367 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] J.Ichihara et al.: "Nucleotide Sequence of the 5'-Flanking Region of the Rat Type II Hexokinase Gene" Biochim.Biophys.Acta. 1260. 365-368 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] E.Majima et al.: "Stabilities of the Fluorescent SH-Reagent Eosin-5-maleimide and Its Adducts with Sulftydryl Compounds" Biochim.Biophys.Acta. 1243. 336-342 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] E.Majima et al.: "Translocation of Loops Regulates Transport Activity of Mitochondrial ADP/ATP Carrier Deduced from Formation of a Specific Intermolecular Disulfide Bridge Catalyzed by Copper-o-Phenanthroline" J.Biol.Chem.270. 29548-29554 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] K.Kogure et al.: "Alteration of Enzyme Function of the Type II Hexokinase C-terminal Half on Replacement of Restricted Regions by Corresponding Regions of Glucokinase" J.Biol.Chem.271. -15236 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Y.Shinohara et al.: "Source of ATP for hexokinase-catalyzed glucose phosphorylation in tumor cells:dependence on the rate of oxidative phosphorylation relative to that of extramitochondrial ATP generation" Biochim.Biophys.Acta. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] 篠原康雄,寺田 弘: "グルコキナーゼ遺伝子の重複融合による高等動物のヘキソキナーゼ遺伝子形成" 生化学. 67. 137-141 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] 山〓尚志,篠原康雄,寺田 弘: "ミトコンドリア輸送タンパク質のスーパーファミリー" 生体の科学. 46. 605-607 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] H.Terada et al.: "Structural Requirements of Leukotriene Antagonists QSAR and Drug Design -New Developments and Applications(T.Fujita,Ed)" Elsevier,Amsterdam. 341-367 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] J.Ichihara et al.: "Nucleotide sequence of the 5′-flanking region of the type 11 hexoinase gene" Biochim.Biophys.Acta. 1260巻. 365-368 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] E.Majima et al.: "Stabilities of the fluorescent SH-reagent eosin-5-maleimide and its adducts with sulfhydryl compounds" Biochim.Biophys.Acta. 1243巻. 336-342 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] E.Majima et al.: "Translocation of loops regulates transport activity of mitochondrial ADP/ATP carrier deduced from formation of a specific intermolecular disulfide bridge catalyzed by copper-o-phenanthroline" J.Biol.Chem.270巻. 29548-29554 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 篠原康雄、寺田 弘: "グルコキナーゼ遺伝子の重複融合による高等動物のヘキソキナーゼ遺伝子の形成" 生化学. 67巻. 137-141 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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