Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016;16(27):3048-3057.
doi: 10.2174/1568026616999160215151704.

Copper Homeostasis for the Developmental Progression of Intraerythrocytic Malarial Parasite

Hiroko Asahi  1 , Fumie Kobayashi, Shin-Ichi Inoue, Mamoru Niikura, Kenji Yagita, Mohammed Essa Marghany Tolba
Affiliations
Review

Copper Homeostasis for the Developmental Progression of Intraerythrocytic Malarial Parasite

Hiroko Asahi et al. Curr Top Med Chem. 2016.

Abstract

Malaria is one of the world's most devastating diseases, particularly in the tropics. In humans, Plasmodium falciparum lives mainly within red blood cells, and malaria pathogenesis depends on the red blood cells being infected with the parasite. Nonesterified fatty acids (NEFAs), including cis-9-octadecenoic acid, and phospholipids have been critical for complete parasite growth in serum-free culture, although the efficacy of NEFAs in sustaining the growth of P. falciparum has varied markedly. Hexadecanoic acid and trans-9-octadecenoic acid have arrested development of the parasite, in association with down-regulation of genes encoding copper-binding proteins. Selective removal of Cu+ ions has blockaded completely the ring-trophozoite-schizont progression of the parasite. The importance of copper homeostasis for the developmental progression of P. falciparum has been confirmed by inhibition of copper-binding proteins that regulate copper physiology and function by associating with copper ions. These data have provided strong evidence for a link between healthy copper homeostasis and successive developmental progression of P. falciparum. Perturbation of copper homeostasis may be, thus, instrumental in drug and vaccine development for the malaria medication. We review the importance of copper homeostasis in the asexual growth of P. falciparum in relation to NEFAs, copperbinding proteins, apoptosis, mitochondria, and gene expression.

PubMed Disclaimer

Figures

Fig. (1)
Fig. (1)
Different stages of P. falciparum cultured synchronously and stained with Giemsa.
Fig. (2)
Fig. (2)
(A) Representative modification of growth of P. falciparum cultured synchronously in the presence of various growth promoters, indicating comparative growth, SS, SMF, and IMI. Each developmental stage was compared with complete growth in GFSRPMI (control): schizonts at 25 h (Schizont-25h), merozoites at 45 h (Released merozoite-45h), ring forms at 45 h (Ring form-45h), and parasitemia at 45 h (Parasitemia-45h). (B) Growth-rate-determining step and growth level in development of P. falciparum cultured in the presence of various NEFAs. C12:0, dodecanoic acid; C14:0, tetradecanoic acid; C22:0, docosanoic acid; C18:1; C18:1-cis-6; C18:1-cis-11; C16:1; C18:2; C20:4; C18:1-trans-9.
Fig. (3)
Fig. (3)
Effect of TTM (A) and neocuproine (B) on growth of synchronized P. falciparum parasite. Synchronized parasites at the ring stage are cultured in the complete medium for 28 h. Each developmental stage is counted after Giemsa staining.
Fig. (4)
Fig. (4)
Growth of P. falciparum co-cultured with infected RBCs and uninfected RBCs that are pretreated separately with TTM (A) and neocuproine (B). The parasite are cultured in the complete medium for 95 h. The growth rate is estimated by dividing the parasitemia of the test sample after 95 h incubation by the initial parasitemia.
See this image and copyright information in PMC

References

    1. World Health Organization (WHO) World Malaria Report. 2014.
    1. Ridley R.G. Medical need, scientific opportunity and the drive for antimalarial drugs. Nature. 2002;415(6872):686–693. - PubMed
    1. Ben Mamoun C., Prigge S.T., Vial H. Targeting the Lipid Metabolic Pathways for the Treatment of Malaria. Drug Dev. Res. 2010;71(1):44–55. - PMC - PubMed
    1. Miotto O., Almagro-Garcia J., Manske M., Macinnis B., Campino S., Rockett K.A., Amaratunga C., Lim P., Suon S., Sreng S., Anderson J.M., Duong S., Nguon C., Chuor C.M., Saunders D., Se Y., Lon C., Fukuda M.M., Amenga-Etego L., Hodgson A.V., Asoala V., Imwong M., Takala-Harrison S., Nosten F., Su X.Z., Ringwald P., Ariey F., Dolecek C., Hien T.T., Boni M.F., Thai C.Q., Amambua-Ngwa A., Conway D.J., Djimde A.A., Doumbo O.K., Zongo I., Ouedraogo J.B., Alcock D., Drury E., Auburn S., Koch O., Sanders M., Hubbart C., Maslen G., Ruano-Rubio V., Jyothi D., Miles A., O'Brien J., Gamble C., Oyola S.O., Rayner J.C., Newbold C.I., Berriman M., Spencer C.C., McVean G., Day N.P., White N.J., Bethell D., Dondorp A.M., Plowe C.V., Fairhurst R.M., Kwiatkowski D.P. Multiple populations of artemisinin-resistant Plasmodium falciparum in Cambodia. Nat. Genet. 2013;45(6):648–655. - PMC - PubMed
    1. Bannister L., Mitchell G. The ins, outs and roundabouts of malaria. Trends Parasitol. 2003;19(5):209–213. - PubMed

LinkOut - more resources