scholarly journals Enhanced choline and Rb+ transport in human erythrocytes infected with the malaria parasite Plasmodium falciparum

1991 ◽  
Vol 278 (2) ◽  
pp. 521-525 ◽  
Author(s):  
K Kirk ◽  
H Y Wong ◽  
B C Elford ◽  
C I Newbold ◽  
J C Ellory
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Parasite ◽  
Human Erythrocytes ◽  
Transport Pathway ◽  
Choline Transport ◽  
Transport Component ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum ◽  
Infected Cells

Human erythrocytes infected in vitro with the malaria parasite Plasmodium falciparum showed a markedly increased rate of choline influx compared with normal cells. Choline transport into uninfected cells (cultured in parallel with infected cells) obeyed Michaelis-Menten kinetics (Km approximately 11 microM). In malaria-parasite-infected cells there was an additional choline-transport component which failed to saturate at extracellular concentrations of up to 500 microM. This component was less sensitive than the endogenous transporter to inhibition by the Cinchona bark alkaloids quinine, quinidine, cinchonine and cinchonidine, but showed a much greater sensitivity than the native system to inhibition by piperine. The sensitivity of the induced choline transport to these reagents was similar to that of the malaria-induced (ouabain- and bumetanide-resistant) Rb(+)-transport pathway; however, the relative magnitudes of the piperine-sensitive choline and Rb+ fluxes in malaria-parasite-infected cells varied between cultures. This suggests either that the enhanced transport of the two cations was via functionally distinct (albeit pharmacologically similar) pathways, or that the transport was mediated by a pathway with variable substrate selectivity.

scholarly journals Organoarsenic Compounds with In Vitro Activity against the Malaria Parasite Plasmodium falciparum

Biomedicines ◽  
2020 ◽  
Vol 8 (8) ◽  
pp. 260
Author(s):  
Sofia Basova ◽  
Nathalie Wilke ◽  
Jan Christoph Koch ◽  
Aram Prokop ◽  
Albrecht Berkessel ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Parasite ◽  
Rapid Development ◽  
Sexual Transmission ◽  
Leukemia Cell ◽  
Leukemia Cell Line ◽  
In Vitro Assays ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum

The rapid development of parasite drug resistance as well as the lack of medications targeting both the asexual and the sexual blood stages of the malaria parasite necessitate the search for novel antimalarial compounds. Eleven organoarsenic compounds were synthesized and tested for their effect on the asexual blood stages and sexual transmission stages of the malaria parasite Plasmodium falciparum using in vitro assays. The inhibitory potential of the compounds on blood stage viability was tested on the chloroquine (CQ)-sensitive 3D7 and the CQ-resistant Dd2 strain using the Malstat assay. The most effective compounds were subsequently investigated for their effect on impairing gametocyte development and gametogenesis, using the gametocyte-producing NF54 strain in respective cell-based assays. Their potential toxicity was investigated on leukemia cell line Nalm-6 and non-infected erythrocytes. Five out of the 11 compounds showed antiplasmodial activities against 3D7, with half-maximal inhibitory concentration (IC50) values ranging between 1.52 and 8.64 µM. Three of the compounds also acted against Dd2, with the most active compound As-8 exhibiting an IC50 of 0.35 µM. The five compounds also showed significant inhibitory effects on the parasite sexual stages at both IC50 and IC90 concentrations with As-8 displaying the best gametocytocidal activity. No hemolytic and cytotoxic effect was observed for any of the compounds. The organoarsenic compound As-8 may represent a good lead for the design of novel organoarsenic drugs with combined antimalarial and transmission blocking activities.

scholarly journals Polymorphism of a high molecular weight schizont antigen of the human malaria parasite Plasmodium falciparum.

1985 ◽  
Vol 161 (1) ◽  
pp. 160-180 ◽  
Author(s):  
J S McBride ◽  
C I Newbold ◽  
R Anand
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Parasite ◽  
Peptide Mapping ◽  
Human Malaria Parasite ◽  
Human Malaria ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum ◽  
Immunological Classification ◽  
Specific Antigens

Intraspecies antigenic diversity in the blood stages of the human malaria parasite Plasmodium falciparum was investigated using a collection of murine monoclonal antibodies and clones of the parasite. The results were as follows: (a) The schizont and merozoite stages of the parasite express on their surface clonally restricted antigens detectable by strain-specific antibodies in indirect immunofluorescence tests. (b) These restricted antigens are phenotypically stable characteristics of clones grown in vitro. (c) The molecules carrying the specific antigens were isolated by immunoprecipitation and were found to be parasite proteins ranging in size from Mr 190,000 to 200,000 between clones. (d) Comparative immunoprecipitation and peptide mapping of these molecules showed that each parasite clone expresses a protein that is antigenically and structurally distinct from the equivalent products of several other clones. (e) The different clonal products are, however, immunologically interrelated, since they possess determinants in common with all tested isolates of the parasite. (f) These polymorphic molecules are closely related to a previously described schizont protein of P. falciparum that is posttranslationally cleaved into fragments located on the merozoite surface. These findings show the existence of a family of related polymorphic schizont antigens (PSA) of P. falciparum, whose expression is clonally restricted, and indicate that these proteins have regions of constant and variable antigenicity. We propose that a system of immunological classification of the parasite can be developed based on the polymorphism of these proteins.

Fine structure of the malaria parasite Plasmodium falciparum in human hepatocytes in vitro

1986 ◽  
Vol 244 (2) ◽  
Author(s):  
JacquesF.G.M. Meis ◽  
P.JosM. Rijntjes ◽  
JanPeter Verhave ◽  
Thivi Ponnudurai ◽  
MichaelR. Hollingdale ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Fine Structure ◽  
Malaria Parasite ◽  
Human Hepatocytes ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum

scholarly journals Increased choline transport in erythrocytes from mice infected with the malaria parasite Plasmodium vinckei vinckei

1998 ◽  
Vol 334 (3) ◽  
pp. 525-530 ◽  
Author(s):  
Henry M. STAINES ◽  
Kiaran KIRK
Keyword(s):  
Malaria Parasite ◽  
Significant Contribution ◽  
Transport Pathway ◽  
Choline Transport ◽  
Parasite Plasmodium ◽  
Broad Specificity ◽  
Plasmodium Vinckei ◽  
Rule Out

Parasitized erythrocytes from mice infected with the murine malaria parasite Plasmodium vinckei vinckei showed a marked increase in the rate of influx of choline compared with erythrocytes from uninfected mice. In contrast, uninfected erythrocytes from P. vinckei-infected animals transported choline at the same rate as those from uninfected mice. The increased influx of choline into parasitized cells was via two discrete routes. One was a saturable pathway with a Km similar to that of the choline carrier of normal erythrocytes but a Vmax approx. 20-fold higher than that observed in uninfected cells. The other was a non-saturable pathway inhibited by furosemide. At choline concentrations within the normal physiological plasma concentration range, the former pathway contributed approx. two-thirds and the latter approx. one-third of the influx of choline into parasitized cells. The characteristics of the furosemide-sensitive pathway were similar to those of a broad-specificity pathway that is induced in human erythrocytes infected in vitro with Plasmodium falciparum. The results of this study rule out the possibility that the induced transport pathway of P. falciparum-infected erythrocytes is an artifact arising in vitro from the long-term culture of parasitized cells and provide evidence that this pathway makes a significant contribution to the uptake of choline into the parasitized cells of malaria-infected animals.

scholarly journals An intrinsic oscillator drives the blood stage cycle of the malaria parasite Plasmodium falciparum

Science ◽  
2020 ◽  
Vol 368 (6492) ◽  
pp. 754-759 ◽  
Author(s):  
Lauren M. Smith ◽  
Francis C. Motta ◽  
Garima Chopra ◽  
J. Kathleen Moch ◽  
Robert R. Nerem ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Parasite ◽  
Blood Stage ◽  
Developmental Cycle ◽  
Cycle Period ◽  
Molecular Signatures ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum ◽  
Cell Variance

The blood stage of the infection of the malaria parasite Plasmodium falciparum exhibits a 48-hour developmental cycle that culminates in the synchronous release of parasites from red blood cells, which triggers 48-hour fever cycles in the host. This cycle could be driven extrinsically by host circadian processes or by a parasite-intrinsic oscillator. To distinguish between these hypotheses, we examine the P. falciparum cycle in an in vitro culture system and show that the parasite has molecular signatures associated with circadian and cell cycle oscillators. Each of the four strains examined has a different period, which indicates strain-intrinsic period control. Finally, we demonstrate that parasites have low cell-to-cell variance in cycle period, on par with a circadian oscillator. We conclude that an intrinsic oscillator maintains Plasmodium’s rhythmic life cycle.

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