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.

scholarly journals Localization of ferrochelatase in Plasmodium falciparum

2004 ◽  
Vol 384 (2) ◽  
pp. 429-436 ◽  
Author(s):  
Sundaramurthy VARADHARAJAN ◽  
B. K. Chandrashekar SAGAR ◽  
Pundi N. RANGARAJAN ◽  
Govindarajan PADMANABAN
Keyword(s):  
Plasmodium Falciparum ◽  
De Novo ◽  
Enzymic Activity ◽  
Malarial Parasite ◽  
Parasite Genome ◽  
Marker Proteins ◽  
Parasite Plasmodium ◽  
Theoretical Predictions ◽  
Parasite Plasmodium Falciparum

Our previous studies have demonstrated de novo haem biosynthesis in the malarial parasite (Plasmodium falciparum and P. berghei). It has also been shown that the first enzyme of the pathway is the parasite genome-coded ALA (δ-aminolaevulinate) synthase localized in the parasite mitochondrion, whereas the second enzyme, ALAD (ALA dehydratase), is accounted for by two species: one species imported from the host red blood cell into the parasite cytosol and another parasite genome-coded species in the apicoplast. In the present study, specific antibodies have been raised to PfFC (parasite genome-coded ferrochelatase), the terminal enzyme of the haem-biosynthetic pathway, using recombinant truncated protein. With the use of these antibodies as well as those against the hFC (host red cell ferrochelatase) and other marker proteins, immunofluorescence studies were performed. The results reveal that P. falciparum in culture manifests a broad distribution of hFC and a localized distribution of PfFC in the parasite. However, PfFC is not localized to the parasite mitochondrion. Immunoelectron-microscopy studies reveal that PfFC is indeed localized to the apicoplast, whereas hFC is distributed in the parasite cytoplasm. These results on the localization of PfFC are unexpected and are at variance with theoretical predictions based on leader sequence analysis. Biochemical studies using the parasite cytosolic and organellar fractions reveal that the cytosol containing hFC accounts for 80% of FC enzymic activity, whereas the organellar fraction containing PfFC accounts for the remaining 20%. Interestingly, both the isolated cytosolic and organellar fractions are capable of independent haem synthesis in vitro from [4-14C]ALA, with the cytosol being three times more efficient compared with the organellar fraction. With [2-14C]glycine, most of the haem is synthesized in the organellar fraction. Thus haem is synthesized in two independent compartments: in the cytosol, using the imported host enzymes, and in the organellar fractions, using the parasite genome-coded enzymes.

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 Effect of polyamine depletion on macromolecular synthesis of the malarial parasite, Plasmodium falciparum, cultured in human erythrocytes

1987 ◽  
Vol 242 (1) ◽  
pp. 221-226 ◽  
Author(s):  
Y G Assaraf ◽  
L Abu-Elheiga ◽  
D T Spira ◽  
H Desser ◽  
U Bachrach
Keyword(s):  
Amino Acids ◽  
Plasmodium Falciparum ◽  
Dna Synthesis ◽  
Rna Synthesis ◽  
Human Erythrocytes ◽  
Malarial Parasite ◽  
Macromolecular Synthesis ◽  
Irreversible Inhibitor ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum

DL-alpha-Difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, prevented the increases in putrescine and spermidine, but not in spermine, in human erythrocytes infected with the malarial parasite Plasmodium falciparum. The addition of putrescine to these polyamine-depleted cultures restored the normal concentrations of spermidine, whereas that of putrescine even exceeded that of the control cultures. DFMO also inhibited the incorporation of radioactive amino acids into the proteins of parasitized erythrocytes. Electrophoresis on polyacrylamide gels revealed that the synthesis of some proteins was completely blocked by DFMO, but the synthesis of others was not affected. DFMO also caused a partial inhibition of RNA synthesis, and DNA synthesis was completely blocked in polyamine-depleted parasitized erythrocytes. It has been suggested that putrescine and/or spermidine are required for the synthesis of certain proteins in parasitized erythrocytes and that at least one of those proteins is related to the synthesis of DNA of the malarial parasite. It appears that polyamines regulate the schizogony process of P. falciparum.

scholarly journals Involvement of spectrin and ATP in infection of resealed erythrocyte ghosts by the human malarial parasite, Plasmodium falciparum.

1982 ◽  
Vol 95 (3) ◽  
pp. 757-762 ◽  
Author(s):  
J A Olson ◽  
A Kilejian
Keyword(s):  
Plasmodium Falciparum ◽  
Inhibitory Effect ◽  
Parasite Infection ◽  
Malarial Parasite ◽  
Erythrocyte Ghosts ◽  
Experimental Conditions ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum ◽  
Resealed Ghosts

Resealed erythrocyte ghosts were prepared under different experimental conditions and were tested in vitro for susceptibility to infection with the human malarial parasite, Plasmodium falciparum. Resealed ghosts, prepared by dialyzing erythrocytes in narrow membrane tubing against low ionic strength buffer that was supplemented with magnesium ATP, were as susceptible to parasite infection as were normal erythrocytes. There was a direct correlation between intraerythrocytic ATP content and susceptibility to parasite infection. Neither MgCl2 nor sodium ATP could be substituted for magnesium ATP in maintaining high intraerythrocytic ATP concentration. When resealed ghosts were loaded with antispectrin IgG, malaria merozoite invasion was inhibited. At an average intracellular antispectrin IgG concentration of 3.5 micrograms/10(8) cells, there was a 35% inhibition of parasite invasion. This inhibition was due to spectrin crosslinking within the resealed ghosts, since the monovalent, Fab' fragments of antispectrin IgG had no inhibitory effect on invasion. These results indicate that the cytoskeleton plays a role in the complex process of merozoite entry into the host erythrocyte.

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 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.

Effects of lysosomotropic detergents on the human malarial parasite plasmodium falciparum in in vitro culture

1989 ◽  
Vol 38 (8) ◽  
pp. 1271-1277 ◽  
Author(s):  
Z.I. Cabantchik ◽  
J. Silfen ◽  
R.A. Firestone ◽  
M. Krugliak ◽  
E. Nissani ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
In Vitro Culture ◽  
Malarial Parasite ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum

scholarly journals Inhibitory effects of erythrocyte membrane proteins on the in vitro invasion of the human malarial parasite (Plasmodium falciparum) into its host cell.

1981 ◽  
Vol 90 (3) ◽  
pp. 563-567 ◽  
Author(s):  
M Perkins
Keyword(s):  
Plasmodium Falciparum ◽  
Membrane Proteins ◽  
Host Cell ◽  
Malarial Parasite ◽  
Glycophorin A ◽  
Low Concentrations ◽  
Parasite Plasmodium ◽  
Erythrocyte Surface ◽  
Parasite Plasmodium Falciparum

The intracellular development of the erythrocytic stage of the malarial parasite (merozoite) is initiated by the attachment of the parasite to the erythrocyte surface. This paper describes an assay system to investigate Plasmodium falciparum merozoite entry into the host cell and reports on three observations regarding this interaction. (a) Merozoites do not invade human erythrocytes treated with either trypsin or neuraminidase, and both enzymes partially cleave glycophorin A, the major erythrocyte surface sialoglycoprotein. (b) A membrane protein fraction containing glycophorin A will, at low concentrations, inhibit the invasion of isolated merozoites into erythrocytes; no other fractions of membrane proteins have appreciable effects on the reinvasion. (c) Merozoites do not reinvade erythrocytes preincubated with F ab' fragments of antibody prepared against glycophorin A. Together, these three observations imply a role for glycophorin A in the attachment of the malarial parasite to the erythrocyte surface.

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