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http://dx.doi.org/10.3347/kjp.2015.53.4.421

Effect of Farnesyltransferase Inhibitor R115777 on Mitochondria of Plasmodium falciparum  

Ha, Young Ran (Division of Integrative Bioscience and Bioengineering, Center for Biofluid and Biomimic Research, Pohang University of Science and Technology)
Hwang, Bae-Geun (Department of Mechanical Engineering, Center for Biofluid and Biomimic Research, Pohang University of Science and Technology)
Hong, Yeonchul (Department of Parasitology, Kyungpook National University School of Medicine)
Yang, Hye-Won (Department of Parasitology, Kyungpook National University School of Medicine)
Lee, Sang Joon (Department of Mechanical Engineering, Center for Biofluid and Biomimic Research, Pohang University of Science and Technology)
Publication Information
Parasites, Hosts and Diseases / v.53, no.4, 2015 , pp. 421-430 More about this Journal
Abstract
The parasite Plasmodium falciparum causes severe malaria and is the most dangerous to humans. However, it exhibits resistance to their drugs. Farnesyltransferase has been identified in pathogenic protozoa of the genera Plasmodium and the target of farnesyltransferase includes Ras family. Therefore, the inhibition of farnesyltransferase has been suggested as a new strategy for the treatment of malaria. However, the exact functional mechanism of this agent is still unknown. In addition, the effect of farnesyltransferase inhibitor (FTIs) on mitochondrial level of malaria parasites is not fully understood. In this study, therefore, the effect of a FTI R115777 on the function of mitochondria of P. falciparum was investigated experimentally. As a result, FTI R115777 was found to suppress the infection rate of malaria parasites under in vitro condition. It also reduces the copy number of mtDNA-encoded cytochrome c oxidase III. In addition, the mitochondrial membrane potential (${\Delta}{\Psi}m$) and the green fluorescence intensity of MitoTracker were decreased by FTI R115777. Chloroquine and atovaquone were measured by the mtDNA copy number as mitochondrial non-specific or specific inhibitor, respectively. Chloroquine did not affect the copy number of mtDNA-encoded cytochrome c oxidase III, while atovaquone induced to change the mtDNA copy number. These results suggest that FTI R115777 has strong influence on the mitochondrial function of P. falciparum. It may have therapeutic potential for malaria by targeting the mitochondria of parasites.
Keywords
Plasmodium falciparum; malaria; mtDNA; farnesyltransferase inhibitor; mitochondria;
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