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Proteome analysis of peroxisomes-Function of novel peroxisomal proteins and pathogenesis of peroxisome disorders

Research Project

Project/Area Number 14370740
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionTOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY

Principal Investigator

IMANAKA Tsuneo  Toyama Med.&Pharm.University, Fac.of Pharm.Sciences, Professor, 薬学部, 教授 (50119559)

Co-Investigator(Kenkyū-buntansha) MORITA Masashi  Toyama Med.&Pharm.University, Fac.of Pharm.Sciences, Research Associate, 薬学部, 助手 (20191033)
OKUMURA Shoji  Toyama Med.&Pharm.University, Fac.of Pharm.Sciences, Associate Professor, 薬学部, 助教授 (60019122)
TANIGUCHI Hisaaki  Tokushima University, Institute for Enzyme Research, Professor, 分子酵素研究センター, 教授 (10257636)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥13,800,000 (Direct Cost: ¥13,800,000)
Fiscal Year 2004: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2003: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 2002: ¥5,800,000 (Direct Cost: ¥5,800,000)
Keywordsperoxisome / proteome analysis / peroxisomal membrane protein / peroxisomal ABC protein / lon protease / peroxin / fatty acid metabolism / peroxisome disorder / 脂肪酸β酸化 / タンパク質の品質管理 / ペルオシソーム / ペルオシソーム膜タンパク質 / Lon プロテアーゼ / Zellweger syndrome / 副腎白質ジストロフィー / ペルオシソームの品質管理 / プロテオーム
Research Abstract

To understand function of peroxisomes and pathogenesis of peroxisome disorders, we performed proteome analysis of rat liver peroxisomes. Further, we investigated function of novel peroxisomal proteins that we identified. Concerning peroxisome disorders, we analyzed fate of an ABC protein, ALDP that is responsible for adrenoleukodystrophy (ALD) in normal and human ALD fibroblasts. As a result, following new findings were obtained.
1.We prepared rat liver peroxiomes by Nycodenz gradient centrifugation and further by immunoisolation using antibody against PMP70. We identified 65 peroxisomal proteins including 5 novel proteins in the peroxisomes by LC/MS/MS analysis after digestion of the protein bands subjected to SDS-PAGE. RAB2, VAP-A, B, which might be involved in peroxisome biogenesis were identified.
2.As novel 5 peroxisomal proteins, peroxisomal isozyme of Ion protease, a bi-functional enzyme containing aminoglycoside transferase and acyl-CoA dehydrogenease domains, a homolog to endozepine-related protein, a tumor-related protein with ribonuclease domain, a homolog of CGI-135 which is required organelle fission were identified.
3.We cloned the human lon protease cDNA and express Lon protease-His in E.coli. We purified the lon protease and found that the enzyme showed ATP-dependent protease activity against denatured proteins
4.We identified 12 peroxin on rat liver peroxisomes. Pex3p was associated with Pex16p and Pex19p and suggested to be important for peroxisomes biogenesis.
5.We found most ALDPs with missense mutations were deficient on peroxiomes of human ALD fibroblasts. In addition, the mutant proteins were found to be degraded rapidly after synthesis by proteasomes.
Roles of novel peroxisomal proteins are now under investigation.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (34 results)

All 2005 2004 2003 2002 Other

All Journal Article (26 results) Book (2 results) Publications (6 results)

  • [Journal Article] Baicalein 5,6,7-trimethyl ether, a flavonoid derivative, stimulates fatty acid β-oxidation in skin fibroblasts of X-linked adrenoleukodystrophy2005

    • Author(s)
      Morita, M. et al.
    • Journal Title

      FEBS Lett. 579

      Pages: 409-414

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 脂質代謝異常と神経疾患2005

    • Author(s)
      守田雅志, 今中常雄
    • Journal Title

      実験医学 23

      Pages: 224-230

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Baicalein 5,6,7-trimethyl ether, a fiavonoid derivative, stimulates fatty acid b-oxidation in skin fibroblasts of X-linked adrenoleukodystrophy.2005

    • Author(s)
      Morita, M. et al.
    • Journal Title

      FEBS Lett. 579

      Pages: 409-414

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Impaired lipid metabolism and neurodegenerative disease. (Japanese)2005

    • Author(s)
      Morita, M., Imanaka, T.
    • Journal Title

      Exp.Med. 23

      Pages: 224-230

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Baicalein 5,6,7-trimethyl ether, a flavonoid derivative, stimulates fatty acid β-oxidation in skin fibroblasts of X-linked adrenoleukodystrophy2005

    • Author(s)
      Morita, M. et al.
    • Journal Title

      FEBS Lett. 579・2

      Pages: 409-414

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Proteomic analysis of rat liver peroxisomes. Presence of peroxisome-s pecific isozyme of Ion protease2004

    • Author(s)
      Kikuchi, M. et al.
    • Journal Title

      J.Biol.Chem. 279

      Pages: 421-428

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Structure-activity relationship of bile acids and bile acid analogs in regard to FXR activation2004

    • Author(s)
      Fujino, T. et al.
    • Journal Title

      J.Lipid Res. 45

      Pages: 132-138

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Domain architecture and activity of human Pex19p, a chaperone-like protein for intracellular trafficking of peroxisomal membrane proteins2004

    • Author(s)
      Shibata, H. et al.
    • Journal Title

      J.Biol.Chem. 279

      Pages: 38486-38494

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Proteomic analysis of rat liver peroxisomes. Presence of peroxisome-specific isozyme of lon protease.2004

    • Author(s)
      Kikuchi, M. et al.
    • Journal Title

      J.Biol.Chem. 279

      Pages: 421-428

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Structure-activity relationship of bile acids and bile acid analogs in regard to FXR activation.2004

    • Author(s)
      Fujino, T. et al.
    • Journal Title

      L.Lipid Res. 45

      Pages: 132-138

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Domain architecture and activity of human Pex19p, a chaperone-like protein for intracellular trafficking of peroxisomal membrane proteins.2004

    • Author(s)
      Shibata, H. et al.
    • Journal Title

      J.Biol.Chem. 279

      Pages: 38486-38494

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Domain architecture and activity of human Pex19p, a chaperone-like protein for intracellular trafficking of peroxisomal membrane proteins2004

    • Author(s)
      Shibata, H. et al.
    • Journal Title

      J.Biol.Chem. 279・37

      Pages: 38486-38494

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Existence of catalase-less peroxisomes in Sf21 insect cells2003

    • Author(s)
      Kurisu, M. et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 306

      Pages: 169-176

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] ATP-dependent transport of bile acid intermediates across rat liver peroxisomal membranes2003

    • Author(s)
      Une, M.et al.
    • Journal Title

      J.Biochem. 134

      Pages: 225-230

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] ペルオキシソームABCタンパク質と脂肪酸代謝2003

    • Author(s)
      柏山恭範, 今中常雄
    • Journal Title

      膜(MEMBRANE) 28

      Pages: 263-270

    • NAID

      130001440819

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Existence of catalase-less peroxisomes in Sf21 insect cells.2003

    • Author(s)
      Kurisu, M. et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 306

      Pages: 169-176

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] ATP-dependent transport of bile acid intermediates across rat liver peroxisomal membranes.2003

    • Author(s)
      Une, M.et al.
    • Journal Title

      J.Biochem. 134

      Pages: 225-230

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Peroxisomal ABC proteins and fatty acid metabolism. (Japanese)2003

    • Author(s)
      Kashiwayama, Y., Imanaka, T.
    • Journal Title

      Membrane 28

      Pages: 263-270

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Peroxisomes are formed from complex membrane structures in Pex6-deficient CHO cells upon genetic complementation2002

    • Author(s)
      Hashiguchi, N. et al.
    • Journal Title

      Mol.Biol.Cell 13

      Pages: 711-722

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Different accumulations of 3-ketoacyl-CoA thiolase precursor in peroxisomes of Chinese hamster ovary cells harboring a dysfunction in the PEX2 protein2002

    • Author(s)
      Huang, Y. et al.
    • Journal Title

      Biochim.Biophys.Acta 1589

      Pages: 273-284

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] ATP binding/hydrolysis by and phosphorylation of peroxisomal ATP-binding cassette proteins PMP70(ABCD3) and adrenoleukodystrophy protein(ABCD1)2002

    • Author(s)
      Tanaka, A.R. et al.
    • Journal Title

      J.Biol.Chem. 277

      Pages: 40142-40147

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Peroxisomes are formed from complex membrane structures in Pex6-deficient CHO cells upon genetic complementation.2002

    • Author(s)
      Hashiguchi, N. et al.
    • Journal Title

      Mol.Biol.Cell 13

      Pages: 711-722

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Different accumulations of 3-ketoacyl-CoA thiolase precursor in peroxisomes of Chinese hamster ovary cells harboring a dysfunction in the PEX2 protein.2002

    • Author(s)
      Huang, Y. et al.
    • Journal Title

      Biochem.Biophys.Acta 1589

      Pages: 273-284

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] ATP binding/hydrolysis by and phosphorylation of peroxisomal ATP-binding cassette proteins PMP70 (ABCD3) and adrenoleukodystrophy protein (ABCD1).2002

    • Author(s)
      Tanaka, A.R. et al.
    • Journal Title

      J.Biol.Chem. 277

      Pages: 40142-40147

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Peroxisomal ABC proteins and fatty acid metabolism. (Japanese)

    • Author(s)
      Kashiwayama, Y., Imanaka, T.
    • Journal Title

      ABC proteins (Veda, K. ed) (Gakkai Syuppan Center) (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 脂質代謝異常と神経疾患

    • Author(s)
      守田雅志, 今中常雄
    • Journal Title

      実験医学 (印刷中)

    • Related Report
      2004 Annual Research Report
  • [Book] ABC蛋白質(第4章ペルオキシソームABC蛋白質と脂肪酸代謝)(植田和光編)2005

    • Author(s)
      柏山恭範, 今中常雄
    • Publisher
      学会出版センター(印刷中)
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] ABC蛋白質(第4章 ペルオキシソームABC蛋白質と脂肪酸代謝)2005

    • Author(s)
      柏山恭範, 今中常雄(植田和光編)
    • Publisher
      学会出版センター(印刷中のため未定)
    • Related Report
      2004 Annual Research Report
  • [Publications] Kikuchi, M. et al.: "Proteomic analysis of rat liver peroxisomes. Presence of peroxisome-specific isozyme of lon protease"J.Biol.Chem.. 279. 421-428 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Fujino, T. et al.: "Structure-activity relationship of bile acids and bile acid analogs in regard to FXR activation"J.Lipid Res.. 45. 132-138 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kurisu, M. et al.: "Existence of catalase-less peroxisomes in Sf21 insect cells"Biochem.Biophys.Res.Commun.. 306. 169-176 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 柏山恭範, 今中常雄: "ペルオキシソームABCタンパク質と脂肪酸代謝"膜(MEMBRANE). 28. 263-270 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hashiguchi, N. et al.: "Peroxisomes are formed from complex membrane structures in Pex6-deficient CHO cells upon genetic complementation"Mol. Biol. Cell. 13. 711-722 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Huang, Y. et al.: "Different accumulations of 3-ketoacyl-CoA thiolase precursor in peroxisomes of Chinese hamster ovary cells harboring a dysfunction in the PEX2 protein"Biochim. Biophys. Acta. 1589. 273-284 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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