Glutathione export from human erythrocytes and Plasmodium falciparum malaria parasites

2012 ◽  
Vol 448 (3) ◽  
pp. 389-400 ◽  
Author(s):  
Margery A. Barrand ◽  
Markus Winterberg ◽  
Frances Ng ◽  
Mai Nguyen ◽  
Kiaran Kirk ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Plasmodium Falciparum Malaria ◽  
Human Erythrocytes ◽  
Multidrug Resistance Proteins ◽  
Resistance Proteins ◽  
Physiological Conditions ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum ◽  
Oxidative Challenge ◽  
New Permeability Pathways

Glutathione export from uninfected human erythrocytes was compared with that from cells infected with the malaria parasite Plasmodium falciparum using two separate methods that distinguish between oxidized (GSSG) and reduced (GSH) glutathione. One involved enzymatic recycling with or without thiol-masking; the other involved rapid derivatization followed by HPLC. Glutathione efflux from uninfected erythrocytes under physiological conditions occurred predominantly as GSH. On exposure of the cells to oxidative challenge, efflux of GSSG exceeded that of GSH. Efflux of both species was blocked by MK571, an inhibitor of mammalian multidrug-resistance proteins. Glutathione efflux from parasitized erythrocytes was substantially greater than that from uninfected erythrocytes. Under physiological conditions, the exported species was GSH, whereas under energy-depleted conditions, GSSG efflux occurred. Glutathione export from parasitized cells was inhibited partially by MK571 and more so by furosemide, an inhibitor of the ‘new permeability pathways’ induced by the parasite in the host erythrocyte membrane. Efflux from isolated parasites occurred as GSH. On exposure to oxidative challenge, this GSH efflux decreased, but no GSSG export was detected. These results are consistent with the view that the parasite supplies its host erythrocyte with GSH, much of which is exported from the infected cell via parasite-induced pathways.

scholarly journals Invasion of mouse erythrocytes by the human malaria parasite, Plasmodium falciparum.

1987 ◽  
Vol 165 (6) ◽  
pp. 1713-1718 ◽  
Author(s):  
F W Klotz ◽  
J D Chulay ◽  
W Daniel ◽  
L H Miller
Keyword(s):  
Plasmodium Falciparum ◽  
Sialic Acid ◽  
Falciparum Malaria ◽  
Vaccine Development ◽  
Plasmodium Falciparum Malaria ◽  
Human Erythrocytes ◽  
Human Malaria Parasite ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum

Plasmodium falciparum malaria merozoites require erythrocyte sialic acid for optimal invasion of human erythrocytes. Since mouse erythrocytes have the form of sialic acid found on human erythrocytes (N-acetyl neuraminic acid), mouse erythrocytes were tested for invasion in vitro. The Camp and 7G8 strains of P. falciparum invaded mouse erythrocytes at 17-45% of the invasion rate of human erythrocytes. Newly invaded mouse erythrocytes morphologically resembled parasitized human erythrocytes as shown on Giemsa-stained blood films and by electron microscopy. The rim of parasitized mouse erythrocytes contained the P. falciparum 155-kD protein, which is on the rim of ring-infected human erythrocytes. Camp but not 7G8 invaded rat erythrocytes, indicating receptor heterogeneity. These data suggest that it may be possible to adapt the asexual erythrocytic stage of P. falciparum to rodents. The development of a rodent model of P. falciparum malaria could facilitate vaccine development.

scholarly journals Organic Osmolyte Permeabilities of the Malaria-induced Anion Conductances in Human Erythrocytes

2004 ◽  
Vol 123 (4) ◽  
pp. 417-426 ◽  
Author(s):  
Christophe Duranton ◽  
Stephan M. Huber ◽  
Valerie Tanneur ◽  
Verena B. Brand ◽  
Canan Akkaya ◽  
...  
Keyword(s):  
Inward Rectifier ◽  
Human Erythrocytes ◽  
Host Cell Membrane ◽  
Waste Products ◽  
Anion Conductance ◽  
Organic Osmolyte ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum ◽  
Flux Measurements ◽  
New Permeability Pathways

Infection of human erythrocytes with the malaria parasite Plasmodium falciparum induces new permeability pathways (NPPs) in the host cell membrane. Isotopic flux measurements demonstrated that the NPP are permeable to a wide variety of molecules, thus allowing uptake of nutrients and release of waste products. Recent patch-clamp recordings demonstrated the infection-induced up-regulation of an inwardly and an outwardly rectifying Cl− conductance. The present experiments have been performed to explore the sensitivity to cell volume and the organic osmolyte permeability of the two conductances. It is shown that the outward rectifier has a high relative lactate permeability (Plactate/PCl = 0.4). Sucrose inhibited the outward-rectifier and abolished the infection-induced hemolysis in isosmotic sorbitol solution but had no or little effect on the inward-rectifier. Furosemide and NPPB blocked the outward-rectifying lactate current and the sorbitol hemolysis with IC50s in the range of 0.1 and 1 μM, respectively. In contrast, the IC50s of NPPB and furosemide for the inward-rectifying current were >10 μM. Osmotic cell-shrinkage inhibited the inwardly but not the outwardly rectifying conductance. In conclusion, the parasite-induced outwardly-rectifying anion conductance allows permeation of lactate and neutral carbohydrates, whereas the inward rectifier seems largely impermeable to organic solutes. All together, these data should help to resolve ongoing controversy regarding the number of unique channels that exist in P. falciparum–infected erythrocytes.

scholarly journals Polyamine levels and the activity of their biosynthetic enzymes in human erythrocytes infected with the malarial parasite, Plasmodium falciparum

1984 ◽  
Vol 222 (3) ◽  
pp. 815-819 ◽  
Author(s):  
Y G Assaraf ◽  
J Golenser ◽  
D T Spira ◽  
U Bachrach
Keyword(s):  
Plasmodium Falciparum ◽  
Human Erythrocytes ◽  
Malarial Parasite ◽  
Biosynthetic Enzymes ◽  
Irreversible Inhibitor ◽  
Trophozoite Stage ◽  
Polyamine Biosynthesis ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum ◽  
Polyamine Content

Human erythrocytes contain only trace amounts of polyamines and lack active polyamine biosynthetic enzymes. A remarkable increase in polyamine content, and in the activity of ornithine and S-adenosyl-L-methionine decarboxylases, is noted in synchronous cultures of the malarial parasite, Plasmodium falciparum. Polyamine biosynthesis reached peak values during the early trophozoite stage, whereas nucleic acid and protein synthesis occurred later in mature trophozoites. DL-alpha-Difluoromethylornithine, an irreversible inhibitor of ornithine decarboxylase, did not interfere with merozoite invasion and with ring-form development, but prevented the transformation of trophozoites to schizonts. Concomitantly, the synthesis of proteins and nucleic acids was significantly inhibited. These inhibitory effects could be readily reversed by the diamine putrescine. Macromolecular synthesis and schizogony were normal when 5-10 mM-DL-alpha-difluoromethylornithine and 0.1 mM-putrescine were added to the cultures simultaneously.

scholarly journals The effect of purified aminoaldehydes produced by polyamine oxidation on the development in vitro of Plasmodium falciparum in normal and glucose-6-phosphate-dehydrogenase-deficient erythrocytes

1986 ◽  
Vol 236 (1) ◽  
pp. 97-101 ◽  
Author(s):  
D M L Morgan ◽  
U Bachrach ◽  
Y G Assaraf ◽  
E Harari ◽  
J Golenser
Keyword(s):  
Plasmodium Falciparum ◽  
Lethal Effect ◽  
Human Erythrocytes ◽  
Malarial Parasite ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum ◽  
Development In Vitro ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Polyamine Oxidation

Purified aminoaldehydes produced by polyamine oxidation were toxic to the malarial parasite, Plasmodium falciparum, cultured in human erythrocytes. There was a profound effect on young ring forms, and, during maturation, parasites became more sensitive to the aldehydes. Oxidation of the aldehydes abolished the lethal effect. The plasmodia within glucose-6-phosphate-dehydrogenase (G6PD)-deficient erythrocytes were more sensitive to mono- and di-aldehydes than were parasites in normal erythrocytes. G6PD-deficient erythrocytes were also more sensitive to pretreatment with the dialdehyde produced by the oxidation of spermine. Pretreatment prevented further invasion by the parasites.

Water and urea transport in human erythrocytes infected with the malaria parasite Plasmodium falciparum

1990 ◽  
Vol 40 (2) ◽  
pp. 269-278 ◽  
Author(s):  
Mary Ann Zanner ◽  
William R. Galey ◽  
Joseph V. Scaletti ◽  
Jesper Brahm ◽  
David L. Vander Jagt
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Parasite ◽  
Human Erythrocytes ◽  
Urea Transport ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum

scholarly journals Solute transport via the new permeability pathways in Plasmodium falciparum–infected human red blood cells is not consistent with a simple single-channel model

Blood ◽  
2006 ◽  
Vol 108 (9) ◽  
pp. 3187-3194 ◽  
Author(s):  
Henry M. Staines ◽  
Stephanie Ashmore ◽  
Hannah Felgate ◽  
Jessica Moore ◽  
Trevor Powell ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Channel Model ◽  
Single Channel ◽  
Membrane Potentials ◽  
Human Red Blood Cells ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum ◽  
Infected Rbcs ◽  
Selective Channel ◽  
New Permeability Pathways

Abstract After infection of a red blood cell (RBC), the malaria parasite, Plasmodium falciparum, increases the permeability of the host's plasma membrane by inducing new permeability pathways (NPPs). Single-channel patch-clamp experiments have shown the presence in infected RBCs of novel anion-selective channel types with low open-state probabilities at positive membrane potentials. These channels have been postulated to form the NPPs. Here, we have used a range of transport techniques to study whether electroneutral solutes use these channels or altered/separate pathways. Transport of the electroneutral solute sorbitol via the NPPs was found to increase by a small but significant amount after gross membrane depolarization. This is inconsistent with transport via a channel with a reduced open-state probability at positive membrane potentials. As has been demonstrated previously for parasite-induced anion currents, sorbitol transport in infected RBCs was found to be sensitive to the presence of bovine serum albumin (BSA). However, it remains to be shown whether the effect is due to serum/BSA altering a single channel type or activating a new pathway. In addition, the study highlights problems that can occur when using different transport techniques to study the NPPs.

scholarly journals CRISPR/Cas9-engineered inducible gametocyte producer lines as a novel tool for basic and applied research on Plasmodium falciparum malaria transmission stages

2020 ◽  
Author(s):  
Sylwia Boltryk ◽  
Armin Passecker ◽  
Arne Alder ◽  
Marga van de Vegte-Bolmer ◽  
Robert Sauerwein ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Applied Research ◽  
Plasmodium Falciparum Malaria ◽  
Mosquito Vector ◽  
Large Numbers ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum ◽  
Invaluable Tool ◽  
Marker Free ◽  
Basic And Applied Research

Abstract The malaria parasite Plasmodium falciparum replicates inside erythrocytes in the blood of infected humans. During each replication cycle, a small proportion of parasites commits to sexual development and differentiates into gametocytes, which are essential for parasite transmission to other human hosts via the mosquito vector. Detailed molecular investigation of gametocyte biology and transmission has been hampered by difficulties in generating large numbers of these highly specialized cells. Here, we engineered marker-free P. falciparum inducible gametocyte producer (iGP) lines for the routine mass production of synchronous gametocytes. Through targeted overexpression of the sexual commitment factor GDV1, iGP lines consistently achieve sexual commitment rates of 75% and produce gametocytes that are infectious to mosquitoes. Subsequent tagging of a nucleoporin allowed us to visualize marked nuclear transformations during gametocytogenesis and demonstrates that further genetic engineering of iGP lines is an invaluable tool for the targeted exploration of gametocyte biology. We believe the iGP approach developed here opens up unprecedented opportunities that will expedite future basic and applied research on P. falciparum transmission stages.

Sign in / Sign up

Export Citation Format

Share Document