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2004 Fiscal Year Final Research Report Summary

Construction and analysis of an electron transport complex II disease model mouse.

Research Project

Project/Area Number 14580801
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory animal science
Research InstitutionTokai University

Principal Investigator

ISHII Naoaki  Tokai University, School of Medicine, Professor, 医学部, 教授 (60096196)

Project Period (FY) 2002 – 2004
KeywordsMitochondria / Electron transport / Complex II / Cytochrome b / Reactive oxygen species / Mouse / Cultured cell / Developmental abnormality
Research Abstract

Much attention has been focused on the hypothesis that oxidative damage plays in cellular and organismal aging. It is known that oxygen is initially converted to superoxide anion (O_2^-), one of reactive oxygen species (ROS), by electron leaked from mainly complex III in the electron transport system present in mitochondria, where it is the major endogenous source of ROS. We have shown that a mutation in a subunit, cytochrome b large subunit (SDHC), of complex II, also results in increasing O_2^- production and therefore lead to apoptosis and precocious aging in C.elegans. Recently, individuals with an inherited propensity for vascularized head and neck tumors (i.e., paragangliomas) have been demonstrated to contain one of several mutations in complex II.
To further explore the role of oxidative stress from mitochondria on aging and cancer, we established a transgenic cell line with a point mutation at the ubiquinone binding region in the SDHC gene. As expected, this mutation increased O_2^- production from complex II and led to excess apoptosis. Moreover, a significant fraction of the surviving cells from the apoptosis were transformed, as evidenced by increased tumor formation after injection into mice. Oxidative stress results in the damage to the cellular components including mitochondria and, therefore leads to apoptosis. Furthermore, oxidative stress must cause mutations in DNA and leads to cancer. It is suggested that oxidative stress from mitochondria play an important role of both apoptosis, which leads to precocious aging, and cancer.
In addition, we constructed the mev-1 transgenic mice. This mutation leads to premature ageing with several phenotypes such as decreasing of muscular power and lost of eyesight. The mev-1 mouse is anticipated as a model animal to understanding the mechanisms of aging and age-related disease by O_2^- from mitochondria.

  • Research Products

    (30 results)

All 2005 2004 2003

All Journal Article (21 results) Book (7 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] A mutation in a cuticle collagen causes hypersensitivity to the endocrine disrupting chemical, bisphenol A, in Caenorhabditis elegans2005

    • Author(s)
      Watanage M
    • Journal Title

      Mutation Research 570

      Pages: 71-80

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A mutation in the SDHC gene of complex II increases oxidative stress, resulting in apoptosis and tumorigenesis2005

    • Author(s)
      Ishii T
    • Journal Title

      Cancer Research 65

      Pages: 203-209

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Direct measurement of oxygen consumption rate on the nematode Caenorhabditis elegans by using an optical technique2005

    • Author(s)
      Suda H
    • Journal Title

      Biochem. Biophys. Res. Comm. 330

      Pages: 839-843

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Effect of oxidative stress on translocation of DAF-16 in oxygen-sensitive mutants, mev-1 and gas-1 of Caenorhabditis elegans2005

    • Author(s)
      Kondo M
    • Journal Title

      Mech. Ageing Develop. 126

      Pages: 637-641

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The p38 signal transduction pathway participates in the oxidative stress-mediated translocation of DAF-16 to Caenorhabditis elegans nuclei2005

    • Author(s)
      Kondo M
    • Journal Title

      Mech. Ageing Develop. 126

      Pages: 642-647

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A mutation in a cuticle collagen causes hypersensitivity to the endocrine disrupting chemical, bishenol A, in Caenorhabditis elegnas2005

    • Author(s)
      Watanabe M
    • Journal Title

      Mutation Research 570

      Pages: 71-80

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Direct measurement of oxygen consumption rate on the nematode Caenorhabditis elegans by using an optical technique2005

    • Author(s)
      Suda H
    • Journal Title

      Biochem.Biophys.Res.Comm. 330

      Pages: 839-843

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Effect of oxidative stress on translocation of DAF-16 in oxygen-sensitive mutants, mev-1 and gas-1 of Caenorhabditis elegans2005

    • Author(s)
      Kondo M
    • Journal Title

      Mech.Aeing Develop 126

      Pages: 637-641

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The p38 signal transduction pathway participates in the oxidative stress-mediated translocation of DAF-16 to Gaenorhabditis elegans nuclei2005

    • Author(s)
      Kondo M
    • Journal Title

      Mech.Ageing Develop. 126

      Pages: 642-647

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Coenzyme Q_<10> can prolong C. elegans lifespan by low ering oxidative stress2004

    • Author(s)
      Ishii N
    • Journal Title

      Mech. Ageing Develop. 125

      Pages: 41-46

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Mitochondrial oxidative stress can lead to nuclear hypermutability2004

    • Author(s)
      Hartman P
    • Journal Title

      Mech. Ageing Develop. 125

      Pages: 417-420

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Mutations in chemosensory cilia cause resistance to paraquat in nematode Caenorhabditis elegans2004

    • Author(s)
      Fujii M
    • Journal Title

      J Biol. Chem. 279

      Pages: 20277-20282

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Coenzyme Q_<10> can prolong C.elegnas lifespan by lowering oxidative stress2004

    • Author(s)
      Ishii N
    • Journal Title

      Mech.Ageing Develop. 125

      Pages: 41-46

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Mitochondrial oxidative stress can lead to nuclear hypermutability2004

    • Author(s)
      Hartman P
    • Journal Title

      Mech.Ageing Develop. 125

      Pages: 417-420

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Mutations in chemosensory cilia cause resistance to paraquat in nematode Caenorhabditis elegans2004

    • Author(s)
      Fujii M
    • Journal Title

      J Biol.Chem. 279

      Pages: 20277-20282

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A complex II defect affects mitochondrial struture, leading to ced-3- and ced-4-dependent apoptosis and aging2003

    • Author(s)
      Senoo-Matsuda N
    • Journal Title

      J. Biol. Chem. 278

      Pages: 22031-22036

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The antibacterial effects of coffee on Escherichia coli and Helicobacter pylori2003

    • Author(s)
      Okabe Y
    • Journal Title

      J. Clin. Biochem. Nutr. 34

      Pages: 85-87

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A complex II defect affects mitochondrial structure, leading to ced-3- and ced-4-dependent apoptosis and aging2003

    • Author(s)
      Senoo-Matsuda N
    • Journal Title

      J.Biol.Chem. 278

      Pages: 22031-22036

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The antibacterial effects of coffee on Escherichia coli and Helicobacter pylori2003

    • Author(s)
      Okabe Y
    • Journal Title

      J.Clin.Biochem.Nutr. 34

      Pages: 85-87

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Electron Transport and Life span in C.elegans2003

    • Author(s)
      Ishii N
    • Journal Title

      Advances in Cell Aging Gerontology (Elsevier)

      Pages: 177-195

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Genetics of aging in the nematode Caenorhabditis elegans2003

    • Author(s)
      Hartman, P
    • Journal Title

      Chromosomal Instability of Aging (Marcel Dekker, Inc.)

      Pages: 493-507

    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] 線虫2003

    • Author(s)
      石井直明
    • Total Pages
      182
    • Publisher
      シュプリンガー
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] 線虫 : ラボマニュアル2003

    • Author(s)
      簗瀬澄乃
    • Total Pages
      224
    • Publisher
      シュプリンガー
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] Advances in Cell Aging Gerontology2003

    • Author(s)
      Ishii N
    • Total Pages
      216
    • Publisher
      Elsevier
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] 老死と不死化2003

    • Author(s)
      石井直明
    • Total Pages
      86
    • Publisher
      自然科学社
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] Chromosomal Instability of Aging2003

    • Author(s)
      Hartman, P
    • Total Pages
      507
    • Publisher
      Marcel Dekker
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] 分子生物学イラストレイテッド2版2003

    • Author(s)
      石井直明
    • Total Pages
      380
    • Publisher
      羊土社
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] 高齢者ケアマニュアル2003

    • Author(s)
      石井直明
    • Total Pages
      340
    • Publisher
      照林社
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] 外来遺伝子の誘導発現の制御が可能な発現ベクター2004

    • Inventor(s)
      石井直明, 石井恭正
    • Industrial Property Rights Holder
      東海大学
    • Industrial Property Number
      特許 2004-183599
    • Filing Date
      2004-06-22
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] 哺乳動物由来の異変SDHC遺伝子を有するトランスジェニック細胞および遺伝子組み換え動物2004

    • Inventor(s)
      石井直明, 石井恭正
    • Industrial Property Rights Holder
      東海大学
    • Industrial Property Number
      特許 101867168(米国出願番号)
    • Filing Date
      2004-06-15
    • Description
      「研究成果報告書概要(和文)」より

URL: 

Published: 2007-12-13  

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