Dynamin like protein 1 participated in the hemoglobin uptake pathway of Plasmodium falciparum  

作　　者：ZHOU Hong-chang GAO Yu-hui ZHONG Xiang WANG Heng 

机构地区：[1]Department of Microbiology and Parasitology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, 5# Dong Dan San Tiao, Rm. 522, Beijing 100005, China

出　　处：《Chinese Medical Journal》2009年第14期1686-1691,共6页中华医学杂志（英文版）

基　　金：This work was supported by the research grants from the National Basic Research Program of China （973 Program, No. 2007CB513100）, the High-Tech Research and Development Program of China （863 Program, No. 2006AA028471）, the China＇s Major Infectious Diseases of Major Special Program （No. 2008ZX10004-011）, and the grant of National Natural Science Foundation of China （No. 30170876）.

摘　　要：Background During the blood stage of malaria infection, parasites internalize in the host red blood cells and degrade massive amounts of hemoglobin for their development. Although the morphology of the parasite＇s hemoglobin uptake pathway has been clearly observed, little has been known about its molecular mechanisms. Methods The recombinant proteins from Plasmodium falciparum, dynamin like protein 1 （PfDYN1） and 2 （PfDYN2） GTPase domain, were expressed in E .coil and showed GTPase activity. By using a dynamin inhibitor, dynasore, we demonstrated the involvement of PfDYN1 in the hemoglobin uptake pathway. Results The GTPase activity of the two recombinant proteins was inhibited by dynasore in vitro. Treatment of parasite cultures with 80 μmol/L dynasore at the ring and early trophozoite stage resulted in substantial inhibition of parasite growth and in an obvious decline of hemoglobin quantum. Furthermore, reduced intracellular hemozoin accumulation and decreased uptake of the FITC-dextran were also observed, together with distinctive changes in the ultrastructure of parasites after the dynasore treatment. Conclusions Our results show that PfDYN1 plays an important role in the hemoglobin uptake pathway of P. falciparum and suggest its possibility of being a novel target for malaria chemotherapy.Background During the blood stage of malaria infection, parasites internalize in the host red blood cells and degrade massive amounts of hemoglobin for their development. Although the morphology of the parasite＇s hemoglobin uptake pathway has been clearly observed, little has been known about its molecular mechanisms. Methods The recombinant proteins from Plasmodium falciparum, dynamin like protein 1 （PfDYN1） and 2 （PfDYN2） GTPase domain, were expressed in E .coil and showed GTPase activity. By using a dynamin inhibitor, dynasore, we demonstrated the involvement of PfDYN1 in the hemoglobin uptake pathway. Results The GTPase activity of the two recombinant proteins was inhibited by dynasore in vitro. Treatment of parasite cultures with 80 μmol/L dynasore at the ring and early trophozoite stage resulted in substantial inhibition of parasite growth and in an obvious decline of hemoglobin quantum. Furthermore, reduced intracellular hemozoin accumulation and decreased uptake of the FITC-dextran were also observed, together with distinctive changes in the ultrastructure of parasites after the dynasore treatment. Conclusions Our results show that PfDYN1 plays an important role in the hemoglobin uptake pathway of P. falciparum and suggest its possibility of being a novel target for malaria chemotherapy.

关 键 词：Plasmodium falciparum hemoglobin uptake DYNAMIN INHIBITOR 

分 类 号：R686[医药卫生—骨科学]