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A basic research on anti-oxidant system of Plasmodium falciparum for its suitability as targets for anti-malarial chemotherapy: In special relation to the parasite peroxiredoxins as the drug targets.

Research Project

Project/Area Number 13670260
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 寄生虫学(含医用動物学)
Research InstitutionResearch Institute, International Medical Center of Japan

Principal Investigator

KAWAZU Shin-ichiro  International Medical Center of Japan, Research Institute, Chief, 研究所, 室長 (60312295)

Co-Investigator(Kenkyū-buntansha) KAWAI Satoru  Dokkyo University, School of Medicine, Instructor, 医学部, 講師 (70275733)
NOZAKI Tomoyoshi  National Institute of Infectious Diseases, Chief, 寄生動物部, 室長 (60198588)
KANO Shigeyuki  International Medical Center of Japan, Research Institute, Director, 研究所, 部長 (60233912)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2001: ¥2,500,000 (Direct Cost: ¥2,500,000)
Keywordsantioxidant / peroxiredoxin / malaria / Plasmodium
Research Abstract

We demonstrated that the 2-Cys peroxiredoxin (2-Cys Prx) from the human malaria parasite P. falciparum can act as a terminal peroxidase of the parasite thioredoxin system. The 2-Cys Prx-null parasite line was more sensitive to superoxide and nitric oxide than wildtype. These findings suggest that the 2-Cys Prx protects the parasite cells from oxidative and nitrosative stresses. A constitutive expression of the 2-Cys Px mRNA, which was depicted by real-time quantitative reverse transcriptase PCR in the intraerythrocytic stage, indicated its fundamental roles in the parasite's antioxidat defense mechanism. The 2-Cys Px protein showed similar expression profile in the intraerythrocytic stage of rodent malaria parasite, P. yoelii. In addition, this Prx protein was expressed in the insect stage (zygote, ookinete and sporozoite) of the rodent malaria parasite.
In contrast, the parasite's 1-Cys Prx mRNA showed a stage-specific expression at the late trophozoite. The trophozoite-specific expression of the Prx protein during the intraerythrocytic and insect stages was confirmed in the rodent malaria parasite. The 1-Cys Prx-overexpressing parasite was less susceptible to chloroquine, which increases heme burden to the parasite cell. The recombinant 1-Cys Prx protein can deal with reactive oxygen species (ROS), emerged from glutathione-induced heme degradation in vitro. An elevated expression of the Prx protein seen in the trophozoite, the stage with active hemoglobin metabolism, suggests an association of this Prx with heme-derived ROS.
Further studies to elucidate such roles of Prx proteins in the malaria parasite may pave the way to utilize the proteins as an alternative targets for the malaria chemotherapy.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Kawazu, s. et al.: "Molecular characterization of a 2-Cys peroxiredoxin from the human malaria parasite Plasmodium falciparum"Mol.Biochem.Parasitol.. 116. 73-79 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mizuno, Y. et al.: "Effect of jasplakinolide on the growth, invasion, and actin cytoskeketon of Plasmodium falciparum"Parasitol.Res.. 88. 844-848 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mizuno, Y. et al.: "In-vitro uptake of vitamin A by Plasmodium falciparum"Ann.Trop.Med.Parasiol.. 97. 237-243 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Komaki-Y, K. et al.: "Disruption of Plasmodium falciparum2-Cys peroxiredoxin gene renders parasites hypersensitive to reactive oxygen and nitorgen species"FEBS Letters. (In printing). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawazu, S. et al.: "Expression profiles of peroxiredoxin proteins of the rodent malaria parasite Plasmodium yoelii"Int.J.Parasitol.. (Revise中). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawazu, S. et al.: "Molecular characterization of a 2-Cys peroxiredoxin from the human malaria parasite Plasmodium falciparum"Mol. Biochem. Parasitol.. 116. 73-79 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mizuno, Y. et al.: "Effect of jasplakinolide on the growth, invasion, and actin cytoskeleton of Plasmodium falciparum"Parasitol. Res.. 88. 844-848 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mizuno, Y. et al.: "In-vitro uptake of vitamin A by Plasmodium falciparum"Ann. Trop. Med. Parasitol.. 97. 237-243 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Komaki-Y, K. et al.: "Disruption of Plasmodium Falciparum2-Cys peroxiredoxin gene renders parasites hypersensitive to reactive oxygen and nitrogen species"FEBS Letters. In printing. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawazu, S. et al.: "Expression profiles of peroxiredoxin proteins of the rodent malaria parasite Plasmodium yoelii"Int. J. Parasitol.. Revising. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hatabu, T. et al.: "The expression system of biologically active canine interleukin-8 in Leishmania promastigotes"Parasitology International. 51. 63-71 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Mizuno, Y. et al.: "Plasmodium falciparum : effect of jasplakinolide on the growth, invasion, and actin cytoskeleton"Parasitology Research. 88. 844-848 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kabututu, Z. et al.: "Prostaglandin production from arachidonic acid andevidence for a 9,11-endoperoxide prostaglandin H(2) reductase in Leishmania"International Journal for. Parasitology. 33. 221-228 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Mizuno, Y et al.: "In-vitro uptake of vitamin A by Plasmodium falciparum"Annals of Tropical Medicine & Parasitology. 97(印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kawazu, S. et al.: "Molecular characterization of a 2-Cys peroxiredoxin from the human malaria parasite Plasmodium falciparum"Molecular and Biochemical Parasitology. 116. 73-79 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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