scholarly journals PLASMEPSIN INHIBITORS; IS PLA2 ENZYME THE NATURAL INHIBITOR IN HUMANS AGAINST PLASMEPSINS PRODUCED BY MALARIAL PARASITE IN THEIR ERYTHROCYTIC CYCLE?

2019 ◽  
Vol 8 (5) ◽  
Author(s):  
Manoj G Tyagi
Keyword(s):  
Red Blood Cells ◽  
Aspartic Acid ◽  
Blood Cells ◽  
Host Cells ◽  
Malarial Parasite ◽  
Plasmodium Parasite ◽  
Malarial Infection ◽  
Erythrocytic Cycle ◽  
Pla2 Enzyme ◽  
Natural Inhibitor

Malaria is a mosquito-borne infectious disease that affects humans and other animals. Most deaths in malarial infection are caused by P. falciparum because P. vivax, P. ovale, and P. malariae generally cause a milder form of malaria. Within the red blood cells, the parasites multiply further, again asexually, periodically breaking out of their host cells to invade fresh red blood cells. Several such amplification cycles occur. Thus, classical descriptions of waves of fever arise from simultaneous waves of merozoites escaping and infecting red blood cells. Plasmepsin is a hemoglobin-degrading enzyme produced by the plasmodium parasite. It is an aspartic acid protease having 2 aspartic acid residues in the active site. On the other hand phospholipase A2 levels are increased in malarial infection and this may possibly provide protection against the effects of plasmepsin. This review examines the importance of this enzyme and interaction with plasmepsin.

Conserved regions from Plasmodium falciparum MSP11 specifically interact with host cells and have a potential role during merozoite invasion of red blood cells

2010 ◽  
Vol 110 (4) ◽  
pp. 882-892 ◽  
Author(s):  
Ana Zuleima Obando-Martinez ◽  
Hernando Curtidor ◽  
Magnolia Vanegas ◽  
Gabriela Arévalo-Pinzón ◽  
Manuel Alfonso Patarroyo ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Potential Role ◽  
Host Cells ◽  
Merozoite Invasion ◽  
Conserved Regions

scholarly journals Heterogeneous timing of asexual cycles in Plasmodium falciparum quantified by extended time-lapse microscopy

2018 ◽  
Author(s):  
Heungwon Park ◽  
Shuqiang Huang ◽  
Katelyn A. Walzer ◽  
Lingchong You ◽  
Jen-Tsan Ashley Chi ◽  
...  
Keyword(s):  
Red Blood Cells ◽  
Blood Cells ◽  
Single Cells ◽  
Time Lapse ◽  
Bimodal Distribution ◽  
Host Cells ◽  
Cycle Period ◽  
Human Red Blood Cells ◽  
Asexual Cycle

ABSTRACTMalarial fever arises from the synchronous bursting of human red blood cells by the Plasmodium parasite. The released parasites re-infect neighboring red blood cells and undergo another asexual cycle of differentiation and proliferation for 48 hours, before again bursting synchronously. The synchrony of bursting is lost during in vitro culturing of the parasite outside the human body, presumably because the asexual cycle is no longer entrained by host-specific circadian cues. Therefore, most in vitro malaria studies have relied on the artificial synchronization of the parasite population. However, much remains unknown about the degree of timing heterogeneity of asexual cycles and how artificial synchronization may affect this timing. Here, we combined time-lapse fluorescence microscopy and long-term culturing to follow single cells and directly measure the heterogeneous timing of in vitro asexual cycles. We first demonstrate that unsynchronized laboratory cultures are not fully asynchronous and the parasites exhibit a bimodal distribution in their first burst times. We then show that synchronized and unsynchronized cultures had similar asexual cycle periods, which indicates that artificial synchronization does not fundamentally perturb asexual cycle dynamics. Last, we demonstrate that sibling parasites descended from the same schizont exhibited significant variation in asexual cycle period, although smaller than the variation between non-siblings. The additional variance between non-siblings likely arises from the variable environments and/or developmental programs experienced in different host cells.

scholarly journals Short-Chain Aliphatic Polysulfonates Inhibit the Entry of Plasmodium into Red Blood Cells

2002 ◽  
Vol 46 (8) ◽  
pp. 2619-2626 ◽  
Author(s):  
Robert Kisilevsky ◽  
Ian Crandall ◽  
Walter A. Szarek ◽  
Shridhar Bhat ◽  
Christopher Tan ◽  
...  
Keyword(s):  
Red Blood Cells ◽  
Sodium Salt ◽  
Blood Cells ◽  
Surface Proteins ◽  
Host Cells ◽  
Short Chain ◽  
Molecular Weight Range ◽  
Antimalarial Agents ◽  
Human Red Blood Cells

ABSTRACT Several steps in the pathogenesis of a Plasmodium falciparum infection depend on interactions of parasite surface proteins with negatively charged sugars on the surface of host cells such as sialate residues or glycosaminoglycans. For these reasons, our previous studies examining agents that interfere with heparan sulfate-protein binding during amyloidogenesis suggested that short-chain aliphatic polysulfonates may prove useful as antimalarial agents. A series of related polysulfonates were synthesized and assessed both in tissue culture with the asexual stages of P. falciparum in human red blood cells and in vivo by use of Plasmodium berghei infections in mice. Poly(vinylsulfonate sodium salt) (molecular weight range, 1,500 to 3,000) proved effective in interfering with P. falciparum merozoite entry into human red blood cells and significantly delaying the increase in the level of P. berghei parasitemia in mice. The concept that anionic molecules that mimic large polysaccharide structures may have antimalarial properties has been suggested and examined previously. Our results suggest that related anionic agents [poly(vinylsulfonate sodium salt)-like molecules] orders of magnitude smaller than those previously considered may prove useful in abrogating merozoite entry into erythrocytes and may potentially block sporozoite entry into liver cells. Structure-activity studies conducted to enhance these properties may provide compounds with scope for significant further analysis and development.

scholarly journals Plasmodium falciparum-infected red blood cells depend on a functional glutathione de novo synthesis attributable to an enhanced loss of glutathione

2000 ◽  
Vol 346 (2) ◽  
pp. 545-552 ◽  
Author(s):  
Kai LÜERSEN ◽  
Rolf D. WALTER ◽  
Sylke MÜLLER
Keyword(s):  
Plasmodium Falciparum ◽  
Red Blood Cells ◽  
Blood Cells ◽  
De Novo ◽  
Specific Inhibitor ◽  
De Novo Synthesis ◽  
Glutamylcysteine Synthetase ◽  
Infected Rbcs ◽  
Erythrocytic Cycle ◽  
Gsh Metabolism

During the erythrocytic cycle, Plasmodium falciparum is highly dependent on an adequate thiol status for its survival. Glutathione reductase as well as de novo synthesis of GSH are responsible for the maintenance of the intracellular GSH level. The first and rate-limiting step of the synthetic pathway is catalysed by γ-glutamylcysteine synthetase (γ-GCS). Using L-buthionine-(S,R)-sulphoximine (BSO), a specific inhibitor of the γ-GCS, we show that the infection with P. falciparum causes drastic changes in the GSH metabolism of red blood cells (RBCs). Infected RBCs lose GSH at a rate 40-fold higher than non-infected RBCs. The de novo synthesis of the tripeptide was found to be essential for parasite survival. GSH depletion by BSO inhibits the development of P. falciparum with an IC50 of 73 μM. The effect of the drug is abolished by supplementation with GSH or GSH monoethyl ester. Our studies demonstrate that the plasmodicidal effect of the inhibitor BSO does not depend on its specificity towards its target enzyme in the parasite, but on the changed physiological needs for the metabolite GSH in the P. falciparum-infected RBCs. Therefore the depletion of GSH is proposed as a chemotherapeutic strategy for malaria, and γ-GCS is proposed as a potential drug target.

scholarly journals Diagnosis of malarial infection using change in properties of optically trapped red blood cells

2017 ◽  
Vol 40 (2) ◽  
pp. 101-105 ◽  
Author(s):  
Apurba Paul ◽  
Ponnan Padmapriya ◽  
Vasant Natarajan
Keyword(s):  
Red Blood Cells ◽  
Blood Cells ◽  
Malarial Infection ◽  
Optically Trapped

The etiology of severe anemia in a village and a periurban area in Mali

Blood ◽  
2004 ◽  
Vol 104 (4) ◽  
pp. 1198-1200 ◽  
Author(s):  
Alassane Dicko ◽  
Amy D. Klion ◽  
Mahamadou A. Théra ◽  
Issaka Sagara ◽  
Daniel Yalcouyé ◽  
...  
Keyword(s):  
Young Children ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Hemoglobin Level ◽  
Severe Anemia ◽  
Malarial Infection ◽  
Major Complications ◽  
Peak Parasitemia ◽  
Infants And Young Children ◽  
Baseline Hemoglobin

Abstract Severe anemia is one of the major complications of malaria in Africa. We studied 2 populations, one in a village and the second in a periurban area in Mali, to understand the preventable factors in the disease. The 2 correlates of disease were parasitemia above 100 000 parasitized red blood cells per microliter (0.1 × 1012/L) and a low baseline hemoglobin level. All cases of moderate to severe anemia occurred in children under 3.2 years of age. Raising the baseline hemoglobin level and lowering peak parasitemia in infants and young children may reduce the incidence of severe anemia resulting from malarial infection. (Blood. 2004;104: 1198-1200)

Freeze-etch studies on the gametocytes of Plasmodium falciparum

1983 ◽  
Vol 41 ◽  
pp. 566-567
Author(s):  
Charles A.M. Meszoely ◽  
Eric F. Erbe ◽  
Russell L. Steere ◽  
Timothy Palmer ◽  
Richard L. Beaudoin
Keyword(s):  
Plasmodium Falciparum ◽  
Life Cycle ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Freeze Fracture ◽  
Malarial Parasite ◽  
Electron Microscopic ◽  
Transmission Electron ◽  
Food Vacuoles ◽  
Ultrathin Sections

The Erythrocytic stages of the Honduras strain of the malarial parasite Plasmodium falciparum were maintained in tissue culture medium RPMI 1640. Red blood cells containing gametocytes and other erythrocytic stages were fixed in 2% glutaraldehyde, and cryoprotected in 30% glycerol in H2O. This preparation was freeze-etched for one minute at -98°C in a modified Denton DFE-2 freeze-etch module. Stereo pairs with specimen tilt of 10 between electron micrographs were obtained with a JEM-100B transmission electron microscope equipped with a 60° top entry goniometer stage.The fine structure of the gametocytes of malarial parasites has been studied by conventional electron microscopic methods [stained ultrathin sections (2 and 3)], but this stage of the life cycle has not been demonstated previously with freeze-fracture studies.Since the red blood cells in our preparation also contained other stages of the life cycle, the following combination of characteristics were used to differentiate the gametocytes: presence of microtubules; food vacuoles; and large size.Microtubules are not found in trophozoites, and merozoites are relatively small and do not contain food vacuoles.

scholarly journals Change in spectrum of Brownian fluctuations of optically trapped red blood cells due to malarial infection

2010 ◽  
Vol 15 (3) ◽  
pp. 037003 ◽  
Author(s):  
Vishal Saraogi ◽  
P. Padmapriya ◽  
Apurba Paul ◽  
Utpal S. Tatu ◽  
Vasant Natarajan
Keyword(s):  
Red Blood Cells ◽  
Blood Cells ◽  
Malarial Infection ◽  
Optically Trapped
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