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Molecular characterization of the tumor specific energy metabolisms

Research Project

Project/Area Number 08457609
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
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) YAMAZAKI Naoshi  Fac.Pharm.Sci.The University of Tokushima Research Associate, 薬学部, 助手 (20271083)
SHINOHARA Yasuo  Fac.Pharm.Sci.The University of Tokushima Associate Professor, 薬学部, 助教授 (60226157)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥8,600,000 (Direct Cost: ¥8,600,000)
Fiscal Year 1997: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1996: ¥5,000,000 (Direct Cost: ¥5,000,000)
Keywordstumor cells / energy metabolism / hexokinase / mitochondria / glycolysis / HIF / glucose transporter / 抗がん剤
Research Abstract

To understand the tumor specific energy metabolisms in a molecular level, we carried out the following studies.
1) know the molecular mechanisms of the transcriptional activation of type II hexokinase gene during carcinogenesis, we analyzed its transcript level under various conditions. As a result, the transcript levels both of HKII and GLUT1 were found to be markedly elevated by low concentration of oxygen. Involvements oftranscriptional factor HIF in the induction of many low oxygen inducible genes are reported. Now we are studying the possible involvement of HIF in the transcriptional control of HKII and GLUT1 during carcinogenesis.
2) to understand the enzyme characteristics of HKII,we made and characte-rized various recombinant proteins. As a result, we succeeded to identify the region which confer sensitivity for glucose-6-phosphate.
3) to understand the physiological meanings of the binding of HKII to mitochondria, we studied the chracteristics of the mt-bound HKII.As a result, binding of HKII to the mitochondrial membrane was found to be very important in the regulatiou of cross talk between oxidative phosphorylation and glycolysis.

Report

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

    (63 results)

All Other

All Publications (63 results)

  • [Publications] K.Kogure et al.: "Alternation of enzyme function of the C-terminal half of type II hexokinase 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
      1997 Final Research Report Summary
  • [Publications] N.Yamazaki et al.: "Isolation and characterization of cDNA and genomic clones encoding human muscle type carnitine palmitoyltransferase I" Biochim.Biophys.Acta. 1307. 157-161 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Ohkura et al.: "Effects of Biscoclaurine Alkaloid Cepharanthine on Newborn Rat Skin Epidermal and Dermal Cells" Bio.Pharm.Bull.19. 495-500 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Ohkura et al.: "Effect of Culture Matrix on Newborn Rat Skin Basal Cells:Modification of Cell Response to Extracellular Calcium" Biol.Pharm.Bull.19. 501-505 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Ohkura et al.: "Polarity of Cultured Newborn rat Skin Basal Cell Layer" Biol.Pharm.Bull.19. 1013-1017 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Ohkura et al.: "Intracellular pH Regulation of Newborn Rat Skin Basal Cells" Biol.Pharm.Bull.19. 1560-1564 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 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 to that of extramitochondrial ATP generation" Biochim.Biophys.Acta. 1319. 319-330 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] N.Yamazaki et al.: "Structural features of the gene encoding human muscle type carnitine palmitoyltransferase I" FEBS Lett.409. 401-406 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] T.Daikoku et al.: "Dramatic enhancement of the specific expression of the heart-type fatty acid binding protein in rat brown adipose tissue by cold exposure" FEBS Lett.410. 383-386 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Takeda et al.: "Longirabdolides E,F and G,6,7-seco-ent-kaurenoids from Rabdosia longituba" Phytochem.45. 785-789 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 安部 一豊、寺田 弘: "活性酸素、フリーラジカルに対する十全大補湯の作用" Natural Medicines. 51. 528-531 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Shinohara et al.: "Quantitative determinations of the steady state transcript levels of hexokinase isozymes and glucose transporter isoforms in normal rat tissues and the malignant tumor cell line AH130" Biochim.Biophys.Acta. 1368. 129-136 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] E.Majima et al.: "Binding of the fluorescein derivative Eosin Y to the mitochondrial ADP/ATP carrier: Characterization of the adenine nucleotide binding site" Biochemistry. 37. 424-432 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Ohkura et al.: "Effect of extracellular calcium on the intercellular calcium level of new born rat skin basal cells" Biol.Pharm.Bull.21. 1-4 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Kogure et al.: "Inhibitory effects of pentamethine trinuclear cyanine dyes on ADP/Fe2+-induced lipidperoxidation in rat liver mitochondria:changes in the mode of action with the hydrophobic nature of the dyes" Biol.Pharm.Bull.21. 180-183 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] S.Goto et al.: "Dynamic structural features of macrocyclic Cytocharasin analogues responsible for their hexose transport inhibition" J.Am.Chem.Soc.,in press.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 木暮 健太朗、上野 雅春、寺田 弘: "DDS技術としてのリポソーム研究の進歩" Fragnance Journal. 66-72 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Terada et al.: "Important role of loops in the transport activity of the mitochondrial ADP/ATP carrier" Progr.Colloid Polym.Sci.106. 192-197 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 篠原 康雄、寺田 弘: "がん細胞のエネルギー代謝系のキャラクタリゼーション" サイエンスリポート、印刷中.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 寺田 弘: "「でぶ」と「やせ」のエネルギー代謝と創薬" 化学と薬学の教室、印刷中.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Kogure et al.: "Alternation of enzyme function of the C-terminal half of type II hexokinase 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
      1997 Final Research Report Summary
  • [Publications] N.Yamazaki et.al.Biochim.: "Isolation and characterization of cDNA and genomic clones encoding human muscle type carnitine palmitoyltransferase I" Biophys.Acta. 1307. 157-161 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Ohkura et al.: "Effects of Biscolaurine Alkaloid Cepharanthine on Newborn Rat Skin Epidermal and Dermal Cells" Bio.Pharm.Bull.19. 495-500 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Ohkura et al.: "Effect of Culture Matrix on Newborn Rat Skin Basal Cells : Modification of Cell Response to Extracellular Calcium" Biol.Pharm.Bull.19. 501-505 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Ohkura et al.: "Polarity of Cultured Newborn rat Skin Basal Cell Layr" Biol.Pharm.Bull.19. 191013-191017 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Ohkura et al.: "Intracellular pH Regulation of Newborn Rat Skin Basal Cells" Biol.Pharm.Bull.19. 1560-1564 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Shinohara et al.: "Source of ATP for hexokinase-catalyzed glucose phosphorylation in tumro cells : Dependence on the rate of oxidative phosphorylation to that of extramitochondrial ATP generation" Biochim.Biophys.Acta. 1319. 319-330 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] N.Yamazaki et al.: "Structural features of the gene encoding human muscle type carnitine palmitoyltransferase I" FEBS Lett. 409. 401-406 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] T.Daikoku et al.: "Dramatic enhancement of the specific expression of the heart-type fatty acid binding protein in rat brown adipose tissue by cold exposure" FEBS Lett.410. 383-386 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Takeda et al.: "Longirabdolides E,F and G,6,7-seco-ent-kaurenoids from Rabdosia longituba" Phytochem.45. 785-789 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Abe and H.Terada: "Radical Scavenging and Antiperoxidative Effect of Jyuzentaihoto" Natural Medicines. 51. 528-531 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Shinohara et al.: "Quantitative determinations of the steady state transcript levels of hexokinase isozymes and glucose transporter isoforms in normal rat tissues and the malignant tumor cell line AH13" Biochim.Biophys.Acta. 1368. 129-136 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] E.Majima et al.: "Binding of the fluorescein derivative Eosin Y to the mitochondrial ADP/ATP carrier : Characterization of the adenine nucleotide binding site" Biochemistry. 37. 424-432 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Ohkura et al.: "Effect of extracellular calcium on the intercellular calcium level of new born rat skin basal cells" Biol.Pharm.Bull.21. 1-4 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Kogure et al.: "Inhibitory effects of pentamethine trinuclear cyanine dyes on ADP/Fe2+induced lipid peroxidation in rat liver mitochondria : changes in the mode of action with the hydrophobic nature of the dyes" Biol.Pharm.Bull.21. 180-183 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] S.Goto et al.: "Dynamic structural features of macrocyclic Cytocharasin analogues respon-sible for their hexose transport inhibition" J.Am.Chem.Soc.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.kogure, M.Ueno and H.Terada: "Advanced research on liposome for drug deliverry system" Fragnance Journal. 66. 72 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Terada et al.: "Important role of loops in the transport activity of the mitochondrial ADP/ATP carrier" Progr.Colloid Polym.Sci.106. 192-197 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Shinohara and H.Terada: "Characterization of energy metabolism specirfic for tumor cells" Science Report. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Y.Shinohara and H.Terada: "Energy metabolism of obese and lean and its application for drug developmental research" Kagaku to Yakugakuno Kyoushitu. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Kogure, et al.: "Alternation of enzyme function of the C-terminal half of type II hexokinase on replacement of restricted regions by corresponding regions of glucokinase" J.Biol.Chem.271. 15230-15236 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] N.Yamazaki, et.al.: "Isolation and characterization of cDNA and genomic clones encoding human muscle type carnitine palmitoyltransferase I" Biochim.Biophys.Acta.1307. 157-161 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Ohkura, et al.: "Effects of Biscoclaurine Alkaloid Cepharanthine on Newborn Rat Skin Epidermal and Dermal Cells" Bio.Pharm.Bull.19. 495-500 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Ohkura, et al.: "Effect of Culture Matrix on Newborn Rat Skin Basal Cells:Modification of Cell Response to Extracellular Calcium" Biol.Pharm.Bull.19. 501-505 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Ohkura, et al.: "Polarity of Cultured Newborn rat Skin Basal Cell Layer" Biol.Pharm.Bull.19. 1013-1017 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Ohkura, et al.: "Intracellular pH Regulation of Newborn Rat Skin Basal Cells" Biol.Pharm.Bull.19. 1560-1564 (1996)

    • Related Report
      1997 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 to that of extramitochondrial ATP generation" Biochim.Biophys.Acta.1319. 319-330 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] N.Yamazaki, et al.: "Structural features of the gene encoding human muscle type carnitine palmitoyltransferase I" FEBS Lett.409. 401-406 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] T.Daikoku, et al.: "Dramatic enhancement of the specific expression of the heart-type fatty acid binding protein in rat brown adipose tissue by cold exposure" FEBS Lett.410. 383-386 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Y.Takeda, et al.: "Longirabdolides E,F and G,6,7-seco-ent-kaurenoids from Rabdosia longituba" Phytochem.45. 785-789 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 安部一豊、寺田 弘: "活性酸素、フリーラジカルに対する十全大補湯の作用" Natural Medicines. 51. 528-531 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Y.Shinohara, et al.: "Quantitative determinations of the steady state transcript levels of hexokinase isozymes and glucose transporter isoforms in normal rat tissues and the malignant tumor cell line AH130" Biochim.Biophys.Acta.1368. 129-136 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] E.Majima, et al.: "Binding of the fluorescein derivative Eosin Y to the mitochondrial ADP/ATP carrier:Characterization of the adenine nucleotide binding site" Biochemistry. 37. 424-432 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Ohkura, et al.: "Effect of extracellular calcium on the intercellular calcium level of new born rat skin basal cells" Biol.Pharm.Bull.21. 1-4 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Kogure, et al.: "Inhibitory effects of pentamethine trinuclear cyanine dyes on ADP/Fe2+-induced lipid peroxidation in rat liver mitochondria:changes in the mode of action with the hydrophobic nature of the dyes" Biol.Pharm.Bull.21. 180-183 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] S.Goto, et al.: "Dynamic structural features of macrocyclic Cytocharasin analogues respon-sible for their hexose transport inhibition" J.Am.Chem.Soc.(in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] 小暮健太朗、上野雅晴、寺田 弘: "DDS技術としてのリポソーム研究の進歩" Fragnance Journal. 66-72 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] H.Terada, et al.: "Important role of loops in the transport activity of the mitochondrial ADP/ATP carrier" Progr.Colloid Polym.Sci.106. 192-197 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 篠原康雄、寺田 弘: "がん細胞のエネルギー代謝系のキャラクタリゼーション" サイエンスリポート、印刷中.

    • Related Report
      1997 Annual Research Report
  • [Publications] 寺田 弘: "「でぶ」と「やせ」のエネルギー代謝と創薬" 化学と薬学の教室、印刷中.

    • Related Report
      1997 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. 15230 (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] H.Terada et al.: "Impotant Role of Loops in the Transport Activity of the Mitochondiral ADP/ATP Carrier" Prog.Colloid Polym.Sci.(in press).

    • Related Report
      1996 Annual Research Report

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

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