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

Int J Mol Sci. 2019 Nov 16;20(22):5769. doi: 10.3390/ijms20225769.

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.

Keywords: Plasmodium falciparum; asexual stages; carbonyl index; protein carbonylation; sickle cell trait.

MeSH terms

  • Electrophoresis, Polyacrylamide Gel
  • Erythrocytes / metabolism*
  • Erythrocytes / parasitology
  • Hemoglobin A / chemistry
  • Hemoglobin A / metabolism
  • Hemoglobin, Sickle / chemistry
  • Hemoglobin, Sickle / metabolism
  • Humans
  • Life Cycle Stages
  • Oxidative Stress
  • Plasmodium falciparum / growth & development*
  • Plasmodium falciparum / metabolism
  • Plasmodium falciparum / pathogenicity
  • Protein Carbonylation
  • Proteome / analysis*
  • Proteome / metabolism
  • Protozoan Proteins / analysis
  • Protozoan Proteins / metabolism
  • Sickle Cell Trait / pathology*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • Hemoglobin, Sickle
  • Proteome
  • Protozoan Proteins
  • hemoglobin AA
  • hemoglobin AS
  • Hemoglobin A