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Comprehensive study on the regulation of metabolism of lipids including long-chain fatty acids and very-long-chain faty acids

Research Project

Project/Area Number 11460044
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 応用微生物学・応用生物化学
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

AMACHI Teruo  graduate school of Agriculture, Kyoto University, Professor, 農学研究科, 教授 (30301245)

Co-Investigator(Kenkyū-buntansha) KIOKA Noriyuki  graduate school of Agriculture, Kyoto University, Assistant, 農学研究科, 助手 (90234179)
UEDA Kazumitsu  graduate school of Agriculture, Kyoto University, Associate Professor, 農学研究科, 助教授 (10151789)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥10,700,000 (Direct Cost: ¥10,700,000)
Fiscal Year 2001: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2000: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1999: ¥4,000,000 (Direct Cost: ¥4,000,000)
Keywordsfatty acids / cholesterol / phospholipids / ABC proteins / transporter / peroxisome / ABCA1 / atherosclerosis / ATP / 遺伝子 / クローニング / ベーター酸化
Research Abstract

This study was done to understand the regulation of metabolism of lipids including long-chain fatty acids, very-long-chain fatty acids, phospholipids, and cholesterol from a comprehensive standpoint. The rate-determining step of catabolic pathway of long-chain fatty acids and very-long-chain fatty acids is the ATP- show high-affinity ATP binding and are co-precipitated together. The are also phosphorylated. Dimer formation could be regulated by ATP binding and/or phosphorylation.
ABCA1 has been suggested to play a key role in cellular lipid release from peripheral cells. In orderto study structure-function relationship of this protein, the protein product of a full-length human ABCA1 cDNA was examined for its functions and topological oreintation. We suggested that the signal peptide in he amino-terminal region is cleaved off in its mature form and that the following large hydrophilic region is exposed to outside of cells unlike previously proposed models.We found that this amino-termibnal extracellular domain contains a segment homologous to he autoantigen SS-N, an epitope of Sjogren's syndrome, and further identified that ABCA7codes for the autoantigen SS-N.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Tanaka, A.R.: "Human ABCA1 contains a Large Amino-Terminal Extracellular Domain Homologous to an Epitope of Sjogren s Syndrome"Biochem. Biophys. Rse. Commun.. 283. 1019-1025 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Chen, Z.: "Reversal of drug resistance mediated by multidrug resistance protein(MRP)1 by dual effects of agosterol a on MRP1 function"Int. J. Cancer. 93. 107-113 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nagata, K.: "Nonequivalent Nucleotide Trapping in the Two Nucleotide binding Folds of the Human Multidrug Resistance Protein MRP1"J. Biol. Chem.. 275. 17626-17630 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Zhao, L.-X.: "Cloning, characterization, and tissue distribution of the ABC transporter ABC2"Biochem, J.. 350. 865-872 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Chen, Z.: "ATP-Dependent efflux of CPT-11 and SN-38 by the multidrug resistance protein (MRP) and its inhibition by PAK-104P"Mol Pharmacol. 55. 921-928 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ueda, K.: "Comparative aspects of the function and mechanism of SUR1 and MDR1 proteins"Biochem. Biophys. Acta. 1461. 305-313 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 稲垣暢也: "ABCトランスポーター -生体防御のABC-遺伝子から疾患まで"診断と治療社. 82 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tanaka, AR.: "Human ABCA1 Contains a Large Amino-Terminal Extracellular Domain Homologous to an Epitope of Sjogren's Syndrome"Biochem Biophys Res Commun. 283. 1019-1025 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Chen, Z.: "Reversal of drug resistance mediated by multidrug resistance protein (MRP) 1 by dual effects of agosterol a on MRP1 function"Int J Cancer. 93. 107-113 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nagata, K.: "Nonequivalent Nucleotide Trapping in the Two Nucleotide Binding Folds of the Human Multidrug Resistance Protein MRP1"J. BioL Chem. 275. 17626-17630 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Zhao, L.-X.: "Cloning, characterization, and tissue distribution of the ABC transporter ABC2"Biochem, J.. 350. 865-872 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Chen, Z.: "ATP-Dependent efflux of CPT-11 and SN-38 by the multidrug resistance protein (MRP) and its inhibition by PAK-104P"Mol Pharmacol. 55. 921-928 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ueda, K.: "Comparative aspects of the function and mechanism of SUR1 and MDR1 proteins"Biochim. Biophys. Acta. 1461. 305-313 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tanaka, A.R.: "Human ABCA1 Contains a Large Amino-Terminal Extracellular Domain Homologous to an Epitope of Sjogren's Syndrome"Biochem. Biophys. Res. Commun.. 283. 1019-1025 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Chen, Z.: "Reversal of drug resistance mediated by multidrug resistance protein (MRP) 1 by dual effects of agosterol a on MRP1 function"Int. J. Cancer. 93. 107-113 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yazaki, K.: "A novel Coptis japonica multidrug resistant protein preferentially expressed in the alkaloid-accumulating rhizome"J. Exp. Bot.. 357. 877-879 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 植田和光: "多剤排出トランスポーターMDR1の分子機構?生体防御のABC"蛋白質 核酸 酵素. 46. 588-595 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 植田和光: "ABCA1蛋白質の構造と機能"The Lipid. 13. 42-48 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 稲垣暢也: "ABCトランスポーター-生体防御のABC-遺伝子から疾患まで"診断と治療社. 82 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Matsuo,M.: "Different binding properties and affinities for ATP and ADP among sulfonylurea receptor subtypes, SUR1.SUR2A.and SUR2B."J.Biol.Chem. 275. 28757-28763 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Matsuo,M.: "Functional analysis of a mutant sulfonylurea receptor, SUR1 - R1420C, that is responsible for persistent hyperinsulinemic hypoglycemia of infancy."J.Biol.Chem.. 275. 41184-41191 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nagata,K: "Nonequivalent Nucleotide Trapping in the Two Nucleotide Binding Folds of the Human Multidrug Resistance Protein MRP1"J.Biol.Chem.. 275. 17626-17630 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tanizawa,Y.: "Genetic analysis of Japanese patients with persistent hyperinsulinemic hypoglycemia of infancy : nucleotide - binding fold - 2 mutation impairs cooperative binding of adenine nucleotides to SUR1"Diabetes. 49. 114-20 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tanabe,K: "Direct Photoaffinity Labeling of Kir6.2 by [γ - 32P] ATP - [γ] 4 - Azidoanilide."Biochem. Biophys. Res. Commun.. 272. 316-319 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Zhao,L.- X.,: "Cloning, characterization, and tissue distribution of the ABC transporter ABC2."Biochem,J.,. 350. 865-872 (200)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ueda,K.: "How do P - glycoprotein and other ABC proteins recognize their substrates? In The first International Conference on Cotrol and Diseases of Sodium Dependent Transportation Proteins and Ion Channels."Amsterdam : Elsevier. 425-428. (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ueda K.: "Recent progress in P-glycoprotein research"Anti-cancer drug design. 14. 115-121 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nakayama T.: "Fungal peroxidase: its structure, function, and application"J. Molecular Catalysis B: Enzymatic. 6. 185-198 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Miyagawa K.: "Purification, characterization, and application of an acid urease from Arthrobacter mobilis"J. Biotechnology. 68. 227-236 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ueda K.: "Comparative aspects of the function and mechanism of SUR1 and MDR1 proteins"Biochim. Biophys. Acta. 1461. 305-313 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ueda K.: "Cooperative binding of ATP and MgADP in the sulfonylurea receptor is modulated by glibenclamide"Proc. Natl. Acad. Sci. USA.. 96. 1268-1272 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 植田和光: "トランスポーター型 ABC タンパク質 P 糖タンパク質"最新医学. 54. 360-365 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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