Sickle Cell Trait Induces Oxidative Damage on Plasmodium falciparum Proteome at Erythrocyte Stages

Abstract

The presence of hemoglobin A-S (HbAS) in erythrocytes has been related to the high production of reactive oxygen species (ROS) and an increased in intracellular oxidative stress that affects the progress of Plasmodium erythrocytic cycle life and attenuates its serious clinical symptoms. Nevertheless, oxidative effects on P. falciparum proteome across the intraerythrocytic cycle in the presence of HbAS traits have not been described yet. Here, an immune dot-blot assay was used to quantify the carbonyl index (C.I) on P. falciparum 3D7 proteome at the different asexual erythrocytic stages. Protein carbonylation on parasites cultivated in erythrocytes from two donors with HbAS increased 5.34 ± 1.42 folds at the ring stage compared to control grown in hemoglobin A-A (HbAA) red blood cells. Whereas at trophozoites and schizonts stages were augmented 2.80 ± 0.52 and 3.05 ± 0.75 folds, respectively. Besides proteins involved in processes of the stress response, recognition and invasion were identified from schizonts carbonylated bands by combining SDS-PAGE with MALDI-TOF-TOF analysis. Our results reinforce the hypothesis that such oxidative modifications do not appear to happen randomly, and the sickle cell trait affects mainly a small fraction of parasite proteins particularly sensitive to ROS.

Sickle Cell Anemia and Babesia Infection

“…Further, it has been shown that parasites are fragile and killed by these HbS polymers. A compelling cause of reduced parasite load in AS and SS RBCs is the extent of oxidative damage which is inherent in these host cells added to the oxidative stress due to parasite growth; the cumulative oxidant damage can cause considerable damage to the host RBC and impairment of parasite development [39]. Interestingly, accumulated reactive oxygen species (ROS)-mediated damage is a common mechanism shared by AS, SS, G6PD-deficient, βand α-thalassemia RBCs in mediating resistance to malaria [40,41].…”

Peroxiredoxin 2: An Important Element of the Antioxidant Defense of the Erythrocyte

“…The hydroperoxides themselves are not very reactive but are readily converted in the presence of free iron and electron donor molecules to alkoxyl and hydroxyl radicals, which indiscriminately inflict damage on biomolecules. Intraerythrocyte parasites produce additional ROS [3,4]. Apart from ROS coming from inside the cells, erythrocytes may be exposed to ROS generated in tissues they contact.…”

“…Intraerythrocyte parasites produce additional ROS [3,4]. Apart from ROS coming from inside the cells, erythrocytes may be exposed to ROS generated in tissues they contact.…”