title: Copper Homeostasis for the Developmental Progression of Intraerythrocytic Malarial Parasite.
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.
authors.affiliation: Division of Tropical Diseases and Parasitology, Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo 181 8611, Japan. isseix20@ks.kyorin-u.ac.jp.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Asahi
authors.forename: Fumie
authors.initials: F
authors.lastname: Kobayashi
authors.forename: Shin-Ichi
authors.initials: SI
authors.lastname: Inoue
authors.forename: Mamoru
authors.initials: M
authors.lastname: Niikura
authors.forename: Kenji
authors.initials: K
authors.lastname: Yagita
authors.forename: Mohammed Essa Marghany
authors.initials: ME
authors.lastname: Tolba
mesh_terms: D000818:Animals; D003300:Copper / Q000378:metabolism*; D016895:Culture Media, Serum-Free; D018450:Disease Progression; D004912:Erythrocytes / Q000469:parasitology*; D006706:Homeostasis; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood / Q000473:pathology; D010963:Plasmodium falciparum / Q000254:growth & development*
chemical_list: D016895:Culture Media, Serum-Free; D003300:Copper