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

Alber Díaz-Castillo,Carlos Moneriz-Pretell,Neyder Contreras-Puentes,Darío Mendez-Cuadro,Ciro Alvear-Sedán,Erika Rodríguez-Cavallo

doi:10.3390/ijms20225769

Alber Díaz-Castillo, Carlos Moneriz-Pretell + Show 4 more

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https://doi.org/10.3390/ijms20225769

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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.

Highlights

Malaria is one of the oldest diseases in the world, during the last 70,000 years of co-evolution with humans it has generated a selective pressure on the human genome and produces the appearance of erythrocyte polymorphisms, such as structural and quantitative hemoglobinopathies [1]
Results obtained for control hemoglobin A-A (HbAA) showed low carbonyl indexes during the ring stage, a maximum of oxidative response in trophozoites, followed by a little decrease during the schizont stage
This behavior is congruent with the development of the parasite, which shows maximum metabolic activity during the trophozoite stage. In this period the parasite consumes hemoglobin and releases pro-oxidant products derived from free heme [23,24]; P. falciparum prevents its deleterious effects by increasing of their efficient antioxidant systems, such as the GluPho enzyme that corresponds to the combination of the G6PD of the parasite with the second enzyme of the pathway of the pentoses, 6-phosphogluconolactonase (PfG6PD-6PGL) [25,26]

Summary

Introduction

Malaria is one of the oldest diseases in the world, during the last 70,000 years of co-evolution with humans it has generated a selective pressure on the human genome and produces the appearance of erythrocyte polymorphisms, such as structural and quantitative hemoglobinopathies [1]. These constitute an important health problem, mainly in malaria-endemic areas with a high frequency of individual carriers, in their countries of tropical and subtropical origin but globally as a result of the augment of massive human migrations [2]. In some geographical regions with a great number of

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