Effect of farnesyltransferase inhibitor on the function of mitochondria of Plasmodium falciparum
© Ha and Lee; licensee BioMed Central Ltd. 2012
Published: 15 October 2012
Malaria is one of the world’s public health problems in terms of medical emergency with a high risk of mortality. The protozoan malaria parasites are transmitted by infected female mosquitoes . The most pathogenic human malaria parasite, Plasmodium falciparum, has gradually expanded in last three decades . Choloroquine is the cheapest and the most widely used drug in almost endemic countries. However, Plasmodium falciparum exhibits resistance to their drug. Resistance to the combination of sulfadoxine-pyrimethamine was also already emerged . Farnesyltransferase have been identified in eukaryotic organisms, including pathgenic protozoa of the genera Plasmodium [3, 4]. Therefore, the inhibition of farnesyltransferase has been suggested as a new strategy for the malaria treatment. However, the exact mechanism of action of this class of agents is still unknown . In addition, the effect of farnesyltransferase inhibitor on malaria mitochondria level is not fully understood. In this study, the effect of farnesyltransferase inhibitor on the function of mitochondria of Plasmodium falciparum were investigated experimentally. The oxygen distribution and the morphological shape of farnesyltransferase inhibitor-treated mitochondria were examined under in vitro condition. From this study, we found farnesyltransferase inhibitor is very important to understand the mitochondrial function of Plasmodium falciparum as an antimalarial drug.
Materials and methods
Culture of malaria parasites.
Synchronization of Plasmodium falciparum.
Determination of oxygen gradients in malaria.
In this study, farnesyltransferase inhibitor was treated to RBCs (Red blood cells) uninfected by Plasmodium falciparum. Farnesyltransferase inhibitor has noticeable effects on mitochondrial function of malaria parasites, compared to the control case for non-infected RBCs.
Oxygen distribution and morphological shape of farnesyltransferase inhibitor-treated mitochondria were investigated under in vitro condition. The farnesyltransferase inhibitor was observed to be very important to understand the mitochondrial function of malaria parasite as an effective antimalarial drug.
This research was supported by the World Class University (WCU) program through the National Research Foundation of Korea, funded by the Ministry of Education, Science, and Technology (MEST, R31 -2008-000-10105-0 or R31-10105) and the Creative Research Initiatives (Center for Biofluid and Biomimic Research) from MEST and from the National Research Foundation (NRF) of Korea.
- Cox FE: History of the discovery of the malaria parasites and their vectors. Parasites & vectors. 2010, 3: 5-10.1186/1756-3305-3-5.View ArticleGoogle Scholar
- Cowman AF, Crabb BS: Invasion of red blood cells by malaria parasites. Cell. 2006, 124: 755-766. 10.1016/j.cell.2006.02.006.View ArticlePubMedGoogle Scholar
- Sidhu AB, Verdier-Pinard D, Fidock DA: Chloroquine resistance in Plasmodium falciparum malaria parasites conferred by pfcrt mutations. Science. 2002, 298: 210-213. 10.1126/science.1074045.PubMed CentralView ArticlePubMedGoogle Scholar
- Chinappi M, Via A, Marcatili P, Tramontano A: On the mechanism of chloroquine resistance in Plasmodium falciparum. PloS one. 2010, 5: e14064-10.1371/journal.pone.0014064.PubMed CentralView ArticlePubMedGoogle Scholar
- Trempus CS, Bishop WR, Njoroge FG, Doll RJ, Battalora MS, Mahler JF, Haseman JK, Tennant RW: Afarnesyl transferase inhibitor suppressesTPA-mediated skin tumor development without altering hyperplasia in the ras transgenic Tg. AC mouse. Molecular carcinogenesis. 2000, 27: 24-33. 10.1002/(SICI)1098-2744(200001)27:1<24::AID-MC5>3.0.CO;2-M.View ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.