1997 Fiscal Year Annual Research Report

細胞のがん化に伴う特徴的な糖代謝経路の形成とその分子機構

Research Project

Project/Area Number	08457609
Research Institution	The University of Tokushima
Principal Investigator	寺田弘徳島大学, 薬学部, 教授 (00035544)
Co-Investigator(Kenkyū-buntansha)	山ざき尚志徳島大学, 薬学部, 助手 (20271083) 篠原康雄徳島大学, 薬学部, 助教授 (60226157)
Keywords	がん細胞 / エネルギー代謝 / ヘキソキナーゼ / ミトコンドリア / 糖代謝 / HIF / 1型糖輸送担体
Research Abstract	我々は、本研究課題に掲げた「細胞のがん化に伴う特徴的な糖代謝経路の形成とその分子機構」を明らかにすることを目的として研究を行い、以下の知見を得た. 1)細胞のがん化に伴うII型ヘキソキナーゼの転写亢進の分子機構本遺伝子とGLUT1の転写レベルが、酸素濃度の低下に伴って協調的に上昇することを見いだした.更に、低酸素によって誘導される遺伝子の転写制御に係る因子hypoxia inducible factor(HIF)のコンセンサス配列が本遺伝子の5'上流に完全に保存されていることを見いだした.現在、II型ヘキソキナーゼの転写レベルの制御におけるHIFの役割について、解析を行っている. 2)II型ヘキソキナーゼの機能的特性の解明 II型アイソザイムの特異的な転写亢進の生理的意味を明らかにするために、大腸菌の発現系を利用し、II型ヘキソキナーゼの機能的特性とこれを決定している構造因子についての解明を試み、グルコース-6ーリン酸感受性をもたらす領域の同定に成功した. 3)II型ヘキソキナーゼのミトコンドリアへの結合の生理的意味の解明ヘキソキナーゼのミトコンドリアへの結合の生理的意味が、ミトコンドリア内での酸化的リン酸化反応とミトコンドリア外での解糖系とのクロストークのコントロールであることを見いだした.

Research Products

(20 results)

All Other

All Publications (20 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)
[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)
[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)
[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)
[Publications] K.Ohkura, et al.: "Polarity of Cultured Newborn rat Skin Basal Cell Layer" Biol.Pharm.Bull.19. 1013-1017 (1996)
[Publications] K.Ohkura, et al.: "Intracellular pH Regulation of Newborn Rat Skin Basal Cells" Biol.Pharm.Bull.19. 1560-1564 (1996)
[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)
[Publications] N.Yamazaki, et al.: "Structural features of the gene encoding human muscle type carnitine palmitoyltransferase I" FEBS Lett.409. 401-406 (1997)
[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)
[Publications] Y.Takeda, et al.: "Longirabdolides E,F and G,6,7-seco-ent-kaurenoids from Rabdosia longituba" Phytochem.45. 785-789 (1997)
[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)
[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)
[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)
[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)
[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)
[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).
[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)
[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)
[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.
[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.

1997 Fiscal Year Annual Research Report

細胞のがん化に伴う特徴的な糖代謝経路の形成とその分子機構

Principal Investigator

寺田 弘 徳島大学, 薬学部, 教授 (00035544)

Research Products

[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)

[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)

[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)

[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)

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

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

[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)

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

[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)

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

[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)

[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)

[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)

[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)

[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)

[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).

[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)

[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)

[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.

[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.

寺田弘徳島大学, 薬学部, 教授 (00035544)

[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)

[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)

[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.

[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.