Analysis of the mitochondrial accumulation of heme precursors for heme biosynthesis

• Project/Area Number: 19770105
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Functional biochemistry
• Research Institution: Keio University (2008); Tokyo Institute of Technology (2007)
• Principal Investigator: KABE Yasuaka Keio University, 医学部, 講師 (20397037)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,880,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2007: ¥1,800,000 (Direct Cost: ¥1,800,000)
• Keywords: ポルフィリン / ヘム生合成 / ミトコンドリア / トランスポーター

Research Abstract

我々が開発してきたナノアフィニティビーズを用いたスクリーニングシステムにより、ヘム前駆体ポルフィリンの新規結合タンパク質として、ミトコンドリア内トランポーターadeninenucleotide transporter(ANT)の同定に成功した。この結合情報を基盤として、経路が不明であったヘム前駆体のミトコンドリア集積機構を明らかとして、ANT がヘム生合成に重要な働きをすることを解明した。

Research Products

• [Journal Article] Capsaicin binds to prohibitin 2 and displaces it from the mitochondria to the nucleus (2009)
  • Author(s): Kuramori C, Azuma M, Kume K, Kaneko Y, Inoue A, Yamaguchi Y, Kabe Y, Hosoya T, Kizaki M, Suematsu M, Handa H
  • Journal Title: Biochem Biophys Res Commun 379(2) Pages: 519-525
  • Peer Reviewed
• [Journal Article] Mono-(2-ethylhexyl) phthalate targets glycogen debranching enzyme and affects glycogen metabolism in rat testis (2009)
  • Author(s): Kuramori C, Hase Y, Hoshikawa K, Watanabe K, Nishi T, Hishiki T, Soga T, Nashimoto A, Kabe Y, Yamaguchi Y, Watanabe H, Kataoka K, Suematsu M, Handa H
  • Journal Title: Toxicol Sci 109(1) Pages: 143-151
  • Peer Reviewed
• [Journal Article] Development and application of high-performance affinity beads : toward chemical biology and drug discovery (2009)
  • Author(s): Sakamoto S, Kabe Y, Hatakeyama M, Yamaguchi Y, Handa H
  • Journal Title: Chem Rec 9(1) Pages: 66-85
  • Peer Reviewed
• [Journal Article] Mono-(2-ethylhexyl) Phthalate Targets Glycogen Debranching Enzyme and Affects Glycogen Metabolism in Rat Testis (2009)
  • Author(s): Chikanori Kuramori
  • Journal Title: Toxicological Science (印刷中)
  • Peer Reviewed
• [Journal Article] A new mechanism of 6-((2-(dimethylamino)ethyl)amino)-3-hyd roxy-7H-indeno(2,1-c)quinolin-7-one dihydrochloride (TAS-103) action discovered by target screening with drug-immobilized affinity beads (2008)
  • Author(s): Yoshida M, Kabe Y, Wada T, Asai A, Handa H
  • Journal Title: Mol Pharmacol 73(3) Pages: 987-994
  • Peer Reviewed
• [Journal Article] Development of a chemical screening system using aqueorin-fused protein (2008)
  • Author(s): Suzuki M, Furukawa S, Kuramori C, Sawa C, Kabe Y, Nakamura M, Sawada J, Yamaguchi Y, Sakamoto S, Inouye S, Handa H
  • Journal Title: Biochem Biophys Res Commun 368(3) Pages: 600-605
  • Peer Reviewed
• [Journal Article] A new APE1/Ref-1-dependent pathway leading to reduction of NF-kappaB and AP-1, and activation of their DNA-binding activity (2008)
  • Author(s): Ando K, Hirao S, Kabe Y, Ogura Y, Sato I, Yamaguchi Y, Wada T, Handa H
  • Journal Title: Nucleic Acids Res 36(13) Pages: 4327-43361
• [Journal Article] Adenine nucleotide translocator transports haem precursors into mitochondria (2008)
  • Author(s): Azuma M*, Kabe Y*, Kuramori C, Kondo M, Yamaguchi Y, Handa H. (*double first authorship)
  • Journal Title: PLoS ONE 3(8) Pages: 3070-3070
  • Peer Reviewed
• [Journal Article] The Ape-1/Ref-1 redox antagonist E3330 inhibits the growth of tumor endothelium and endothelial progenitor cells : therapeutic implications in tumor angiogenesis (2008)
  • Author(s): Zou GM, Karikari C, Kabe Y, Handa H, Anders RA, Maitra A
  • Journal Title: J Cell Physiol 219(1) Pages: 209-218
  • Peer Reviewed
• [Journal Article] Atrazine binds to F1F0-ATP synthase and inhibits mitochondrial function in sperm (2008)
  • Author(s): Hase Y, Tatsuno M, Nishi T, Kataoka K, Kabe Y, Yamaguchi Y, Ozawa N, Natori M, Handa H, Watanabe H
  • Journal Title: Biochem Biophys Res Commun 366(1) Pages: 66-72
  • Peer Reviewed
• [Journal Article] Adenine nucleotide translocator transports haem precursors into mitochondria (2008)
  • Author(s): Motoki Azuma
  • Journal Title: PLos ONE 27 Pages: 3070-3076
  • Peer Reviewed
• [Journal Article] A new APE1/Ref-1-dependent pathway leading to reduction of NF-kappa B and AP-1, and activation of their DNA-binding activity (2008)
  • Author(s): Kozue Ando
  • Journal Title: Nucleic Acid Research 36 Pages: 4327-4336
  • Peer Reviewed
• [Journal Article] A new mechanism of 6-((2-(dimethylaimino)ethyl)amino)-3-hydroxy-7H-ind.eno(2,l-c)quiiiolin-7-one dihydrochloride (TAS-103) acti on discovered by target screening with drug-immobilized affinitv beads. (2008)
  • Author(s): Makoto Yoshida
  • Journal Title: Molecular Phamacology 73 Pages: 987-994
  • Peer Reviewed
• [Journal Article] The enteropathogeni E. coli effector EspB facilitates microvillus effacing and antiphagocytosis by inhibiting myosin function (2007)
  • Author(s): Iizumi Y, Sagara H, Kabe Y, Azuma M, Kume K, Ogawa M, Nagai T, Gillespie PG, Sasakawa C, Handa H
  • Journal Title: Cell Host Microbe 2(6) Pages: 383-392
  • Peer Reviewed
• [Journal Article] The enteropathogenic E.coli effector EspB facilitates microvillus effacing and antiphagocytosis by inhibiting myosin function (2007)
  • Author(s): Yousuke Iizumi
  • Journal Title: Cell Host&Microbe 2 Pages: 383-392
  • Peer Reviewed
• [Journal Article] Atrazine binds to F1F0-ATP synthase and inhibits mitochondrial function in sperm. (2007)
  • Author(s): Yasuyoshi Hase
  • Journal Title: Biochem Biophys Res Commun. 366 Pages: 66-72
  • Peer Reviewed
• [Presentation] HSP27 を介したヘム毒性に対する生体防御機構 (2008)
  • Author(s): 加部泰明
  • Organizer: 第31 回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] HSP27を介したヘム毒性に対する細胞防御機構 (2008)
  • Author(s): 加部泰明
  • Organizer: 第31回日本分子生物学学会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2008-12-09
• [Presentation] 赤血球分化におけるヘム毒性に対する生体防御機構 (2008)
  • Author(s): 加部泰明
  • Organizer: 第3回ケミカルバイオロジー学会
  • Place of Presentation: 東京
  • Year and Date: 2008-06-18
• [Presentation] ヘム刺激による赤血球分化における細胞防御機構の解析 (2007)
  • Author(s): 加部泰明
  • Organizer: 第30 回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-14
• [Presentation] ヘム刺激による赤血球分化における細胞防御機構の解析 (2007)
  • Author(s): 加部 泰明
  • Organizer: 日本分子生物学会
  • Place of Presentation: 横浜みなと未来
  • Year and Date: 2007-12-14
• [Presentation] ヘム生合成に関わるヘム前駆体のミトコンドリア集積機構の解析 (2007)
  • Author(s): 加部泰明
  • Organizer: 第3回ケミカルバイオロジー学会
  • Place of Presentation: 京都
  • Year and Date: 2007-05-09
• [Book] Novel application of affinity beads (2009)
  • Author(s): Yausaki Kabe, Mamoru Hatakeyama, Kousuke Nishio and Hiroshi Handa
  • Publisher: 「Chemical Biology/Chemical Genetics」CMC press(in press)
• [Book] Protein Targeting with Small Molecules : Chemical Biology Techniques and Applications (2009)
  • Author(s): Yasuaki Kabe
  • Publisher: John Wiley & Sons, Inc.(印刷中)
• [Book] Chemical Biology/Chemical Genetics (2008)
  • Author(s): Yasuaki Kabe
  • Publisher: CMC press
• [Book] ナノアフィニティ磁性ビーズを用いたケミカルバイオロジー戦略、蛋白質核酸酵素 (2007)
  • Author(s): 加部泰明、半田宏
  • Publisher: 共立出版