title: Roles of 1-Cys peroxiredoxin in haem detoxification in the human malaria parasite Plasmodium falciparum.
abstract: In the present study, we investigated whether Plasmodium falciparum 1-Cys peroxiredoxin (Prx) (Pf1-Cys-Prx), a cytosolic protein expressed at high levels during the haem-digesting stage, can act as an antioxidant to cope with the oxidative burden of haem (ferriprotoporphyrin IX; FP). Recombinant Pf1-Cys-Prx protein (rPf1-Cys-Prx) competed with glutathione (GSH) for FP and inhibited FP degradation by GSH. When rPf1-Cys-Prx was added to GSH-mediated FP degradation, the amount of iron released was reduced to 23% of the reaction without the protein (P < 0.01). The rPf1-Cys-Prx bound to FP-agarose at pH 7.4, which is the pH of the parasite cytosol. The rPf1-Cys-Prx could completely protect glutamine synthetase from inactivation by the dithiothreitol-Fe(3+)-dependent mixed-function oxidation system, and it also protected enolase from inactivation by coincubation with FP/GSH. Incubation of white ghosts of human red blood cells and FP with rPf1-Cys-Prx reduced formation of membrane associations with FP to 75% of the incubation without the protein (P < 0.01). The findings of the present study suggest that Pf1-Cys-Prx protects the parasite against oxidative stresses by binding to FP, slowing the rate of GSH-mediated FP degradation and consequent iron generation, protecting proteins from iron-derived reactive oxygen species, and interfering with formation of membrane-associated FP.
authors.affiliation: Research Institute, International Medical Center of Japan, Toyama, Tokyo, Japan. skawazu@ri.imcj.go.jp
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Kawazu
authors.forename: Nozomu
authors.initials: N
authors.lastname: Ikenoue
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takemae
authors.forename: Kanako
authors.initials: K
authors.lastname: Komaki-Yasuda
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kano
mesh_terms: D000818:Animals; D005978:Glutathione / Q000378:metabolism; D006418:Heme / Q000378:metabolism*; D007501:Iron / Q000378:metabolism; D010544:Peroxidases / Q000378:metabolism*; D054464:Peroxiredoxins; D010963:Plasmodium falciparum / Q000378:metabolism*
chemical_list: D006418:Heme; D007501:Iron; D010544:Peroxidases; D054464:Peroxiredoxins; D005978:Glutathione