2002 Fiscal Year Final Research Report Summary
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.
| Project/Area Number |
13670260
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
寄生虫学(含医用動物学)
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| Research Institution | Research Institute, International Medical Center of Japan |
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Principal Investigator |
KAWAZU Shin-ichiro International Medical Center of Japan, Research Institute, Chief, 研究所, 室長 (60312295)
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| 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)
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| Project Period (FY) |
2001 – 2002
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| Keywords | antioxidant / peroxiredoxin / malaria / Plasmodium |
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| 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.
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Research Products
(10 results)
