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Mechanism of transcription of phospholipid glutathione peroxidase

Research Project

Project/Area Number 10672052
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 Science, Professor, 薬学部, 教授 (00119603)

Co-Investigator(Kenkyū-buntansha) IMAI Hirotaka  Kitasato University, School of Pharmaceutical Science, 薬学部, 講師 (50255361)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsglutathione peroxidase / mitochondria / infertile / genome / 過酸化脂質 / 抗酸化酵素
Research Abstract

Non-mitochondrial PHGPx was highly expressed in somatic cells such as kidney cells and L929 cells, while the expression of mitochondrial PHGPx was quite low in these cells. Expression of mitochondrial PHGPx was initiated in the 3 weeks development-stage of testis of mice. However, expression of mitochondrial PHGPx was not induced in kidney. Activity of promoter of mitochondrial PHGPx was almost one third of that of total PHGPx. The region of core promoter of mitochondrial PHGPx was the region from -233 to -158 which included SP1 site. While core promoter of non-mitochondrial PHGPx was found in the region from -176 to -56 in which NFY site, CCAAT box and AP2 site.
PHGPx was intensely expressed in mitochondria in the mid-piece of human spermatozoa. We found a dramatic decrease in the level of expression of PHGPx in the spermatozoa of some infertile males. These individuals accounted for about 10% of the group of 73 infertile males that we examined. All seven patients with PHGPx-defective spermatozoa were classified as suffering from oligo-asthenozoospermia, a defect in which both the number and the motility of spermatozoa are significantly below normal. Males with PHGPx-defective spermatozoa accounted for 35% of the 27 infertile males with oligo-asthenozoospermia. No defects in expression of PHGPx in spermatozoa were observed in 31 fertile volunteers. Ultrastructual analysis of mitochondria by electron microscopy demonstrated that the morphology of mitochondria in PHGPx-defective spermatozoa was abnormal. The results suggest that failure of the expression of mitochondrial PHGPx in spermatozoa might be one of the causes of oligo-asthenozoospermia in infertile men.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Arai,M. et al.: "Mitochondrial Phospholipid Hydroperoxide Glutathione Peroxidase (PHGPx) Play a Major Role in Preventing Oxidative Injury to Cells"J.Biol.Chem.. 274. 4924-4933 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakagawa,Y. et al.: "Novel functions of mitochondrial PHGPx as an anti-apoptosic factor."J.Health Science. 46. 414-417 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Imai,H. et al.: "Failure of the the Expression of Phospholipid Hydroperoxide Glutathione Peroxidase in the Spermatozoa of Human Infaile Males"Biology of Reproduction. 64. 674-683 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Arai M., Imai H., Koumura T., Madoka Y., Emoto K., Umeda M., Chiba N.and Nakagawa Y.: "Mitochondrial Phospholipid Hydroperoxide Glutathione Peroxidase (PHGPx) Play a Major Role in Preventing Oxidative Injury to Cells"J.Biol.Chem.. 274. 4924-4933 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakagawa, Y.and Imai, H.: "Novel functions of mitochondrial phospholipid hydroperoxide glutathione peroxidase (PHGPx) as an anti-apoptosic factor."J.Health Science. 46. 414-417 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Imai, H., Suzuki, K., Ishizaka, K., Ichinose, S., Oshima, H., Okayasu, I., Emoto, K., Umeda, M.and Nakagawa, Y.: "Failure of the the Expression of Phospholipid Hydroperoxide Glutathione Peroxidase in the Spermatozoa of Human Infaile Males"Biology of Reproduction. 64. 674-683 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nomura,K. et al.: "Mitochondrial PHGPx inhibits the release of cytochrome c from mitochondria by supressing the peroxidation of cardiolipin in hypoglysaemia-induced apoptosis"Biochem.J.. 351. 183-193 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakagawa,Y. et al.: "Novel functions of mitochondrial PHGPx as an anti-apoptosic factor."J.Health Science. 46. 414-417 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Imai,H. et al.: "Failure of the the Expression of Phospholipid Hydroperoxide Glutathione Peroxidase in the Spermatozoa of Human Infaile Males"Biology of Reproduction. 64. 674-683 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] K. Nomura. et. al.: "Mitochondrial Phospholipid Hydroperoxide Glutathione Peroxidase Suppresses Apoptosis Mediated by a Mitochondrial Death Pathway"J. Biol. Chem.. 274. 29294-29302

    • Related Report
      1999 Annual Research Report
  • [Publications] H.Imai et.al.: "Suppresion of leukotriene formation in RBL-2H3 cells that overexpressed PHGPx." J.Biol.Chem.273. 1990-1997 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] M.Arai.et.al.: "Mitochondrial PHGPx plays a major role in preventing oxidative injury to cells." J.Biol.Chem.274. 4924-4993 (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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