Premium
Roles of 1‐Cys peroxiredoxin in haem detoxification in the human malaria parasite Plasmodium falciparum
Author(s) -
Kawazu Shinichiro,
Ikenoue Nozomu,
Takemae Hitoshi,
KomakiYasuda Kanako,
Kano Shigeyuki
Publication year - 2005
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2005.04611.x
Subject(s) - glutathione , peroxiredoxin , biochemistry , plasmodium falciparum , dithiothreitol , cytosol , cysteine , chemistry , antioxidant , reactive oxygen species , protein degradation , biology , enzyme , immunology , malaria , peroxidase
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.