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The mechanism of protection of apoptosis by the mitochondrial PHGPx

Research Project

Project/Area Number 14572063
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionKitasato University

Principal Investigator

NAKAGAWA Yasuhito  Kitasato University, School of Pharmaceutical Sciences, Professor, 薬学部, 教授 (00119603)

Co-Investigator(Kenkyū-buntansha) KOUMURA Tomoko (HIROTAKA Imai)  Kitasato University, School of Pharmaceutical, Research Associate, 薬学部, 助手 (30337985)
今井 浩孝  北里大学, 薬学部, 助教授 (50255361)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥2,500,000 (Direct Cost: ¥2,500,000)
Keywordscardiolipin / mitochondria / glutathione peroxidase / cytochrome c / apoptosis / 核小体 / EPA / AIF / シトクロームc / 脂質過酸化 / ANT
Research Abstract

In this project, we try to find out the mechanism of the protection of apoptosis mitochondrial type of phospholipid hydroperoxide glutathione peroxidase (PHGPx). Apoptosis caused by 2deoxyglucose was completely suppressed by the overexpression of mitochondrial PHGPx. The release of cytochrome c (cyt.c) provide the irreversible signal of apoptosis. Overexpression of mitochondrial PHGPx inhibit the release of cyt.c from mitochondria. There are two steps for the liberation of cyt. C from mitochondria. First step is the dissociation of cyt.c from inner membrane of mitochondria and second step is the passage of free cyt. C through the permeability transition pore (PT pore) which regulates the opening by adenine nucleotide translocator (ANT).
Cyt.c preferentially binds to the monolayer of cardiolipin which is the specific phospholipid in mitochondria. Binding of cyt.c to CL monolayer significantly decreased by the autooxidation of CL. Cyt.c released from liposome containing CL by the peroxidation with radical initiator, these results suggest that cytc could release from inner membrane of mitochondoria.
ANT activity was significantly decreased by the induction of apoptosis. Inactivation of ANT was well correspond to the liberation of cyt. C from mitochondria. ANT activity of mitochondria markedly inhibited by the fusion of CLOOH with isolated mitochondria suggesting that CLOOH could inhibit ANT activity. ANT activity of reconstituted proteoliposome was suppressed by the addition of CLOOH in proteoliposome.
These results suggest that peroxidation of CL as a mitochondrial specific phospholipid might be a key step to initiate the apoptosis.

Report

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

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Sakamoto, H.: "Overexpression of phospholipid hydroperoxide glutathione peroxidase modulates acetyl-CoA : l-O-alkyl-2-lyso-sn-glycero-3-phosphocholine acetyltransferase activity"J.Biol.Chem.. 277(52). 50431-50438 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kitahara, J.: "Alteration of gene expressions by the overexpression of mitochondrial phospholipid hydroperoxide glutathione peroxidase (mtPHGPx)"Gene Expression. 11. 77-83 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakamura, T.: "Molecular cloning and functional expression of nucleolar phospholipid hydroperoxide glutathione peroxidase in mammalian cells"Biochem.Biophys.Res.Commun.. 311. 139-148 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Imai, H: "Early embryonic lethality caused by targeted disruption of the mouse PHGPx gene."Biochem.Biophys.Res.Commun. 305. 278-286 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Imai, H.: "Protection from inactivation of the adenine nucleotide translocator during hypoglycemia-induced apoptosis by mitochondrial phospolipid hydroperoxide glutathione peroxidase"Biochem.J.. 371. 1-11 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Imai, H.: "Biological significance of phospholipid hydroperoxide glutathione peroxidase (PHGPx, GPx4) in mammalian cells."Free Radic.Bio.Med.. 34(2). 145-169 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakagawa, Y.: "Role of mitochondrial phospholipid hydroperoxide glutathione peroxidase (PHGPx) as a antiapoptotic factor"Biol.Pharm.Bull.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sakamoto, H., Tosaki, T., Nakagawa, Y.: "Overexpression of phospholipid hydroperoxide glutathione peroxidase modulates acetyl-CoA : 1-O-alkiyl-2-lyso-sn-glycero-3-phosphocholine acetyltransferase activity"J.Biol.Chem.. 277(52). 50431-50438 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kitahara, J., Chiba, N., Sakamoto, H., Nakagawa, Y.: "Alteration of gene expressions by the overexpression of mitochondrial phospholipid hydroperoxide glutathione peroxidase (mtPHGPx)"Gene Expression. 11. 77-83 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakamura, T., Imai, H., Tsunashima, N., Nakagawa, Y.: "Molecular cloning and functional expression of nucleolar phospholipid hydroperoxide glutathione peroxidase in mammalian cells"Biochemical and Biophysical Research Communications. 311. 139-148 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Imai, H., Hirao, F., Sakamoto, T., Sekine, K., Mizukura, Y., Saito, M., Kitamoto, T, Hayasaka, M., Hanaoka, K., Nakagawa, Y.: "Early embryonic lethality caused by targeted disruption of the mouse PNGPx gene."Biochemical and Biophysical Research Communications. 305. 278-286 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] lmai, H., Koumura, T., Nakajima, Ryo., Nomura, K., Nakagawa, Y.: "Protection from inactivation of the adenine nucleotide translocator during hypoglycemia-induced apoptosis by mitochondria) phospholipid hydroperoxide glutathione peroxidase"Biochem.J. 371. 1-11 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] lmai, H., Nakagawa, Y.: "Biological significance of phospholipid hydroperoxide ~ glutathione peroxidase (PI-1GPx, GPx4) in mammalian cells."Free Radic.Biol.Med.. 34(2). 145-169 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakagawa, Y.: "Role of ~mitochondrial phospholipid hydroperoxide glutathione peroxidase (PHGPx) as a antiapoptotic factor"Biol.Plzarm.Bull.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Imai H, Koumura T, Nakajima R, Nomura K, Nakagawa Y.: "Protection from inactivation of the adenine nucleotide translocator during hypoglycemia-induced apoptosis by mitochondrial phospholipid hydroperoxide glutathione peroxidase."Biochem J. 371. 1-11 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakamura, T., Imai, H., Tsunashima, N., Nakagawa, Y.: "Molecular cloning and functional expression of nucleolar phospholipid hydroperoxide glutathione peroxidase in mammalian cells"Biochemical and Biophysical Research Communications. 311. 139-148 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Imai, H., Hirao, F., Sakamoto, T., Sekine, (中5人省略), Nakagawa, Y.: "Early embryonic lethality caused by targeted disruption of the mouse PHGPx gene."Biochemical and Biophysical Research Communications. 305. 278-286 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Imai H, Koumura T, Nakajima R, Nomura K, Nakagawa Y: "Protection from inactivation of the adenine nucleotide translocator during hypoglycemia-induced apoptosis by mitochondrial phospholipid hydroperoxide glutathione peroxidase"Biochem J. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Imai, H., Nakagawa, Y: "Biological significance of phospholipid hydroperoxide glutathione peroxidase (PHGPx, GPx4) in mammalian cells"Free Radic. Biol. Med.. 34(2). 145-169 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Imai, H., Suzuki, K., Ishizaka, K., (中5人省略), Nakagawa, Y: "Failure of the Expression of Phospholipid Hydroperoxide Glutathione Peroxidase in the Spermatozoa of Human Infertile Males"Biology of Reproduction. 64. 674-683 (2001)

    • Related Report
      2002 Annual Research Report

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

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