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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malaria-infected red cells and free parasites have limited capabilities for the biosynthesis of amino acids. Therefore, the principal amino acid sources for parasite protein synthesis are the plasma free amino acids and host cell haemoglobin. Infected cells and plasmodia incorporate exogenously supplied amino acids into protein. However, the hypothesis that amino acid utilization (from an external source) is related to availability of that amino acid in haemoglobin is without universal support: it is true for isoleucine and for Plasmodium knowlesi and P. falciparum, but not for methionine, cysteine, and other amino acids, and it does not apply to P. lophurae. More by default than by direct evidence, haemoglobin is believed to be the main amino acid reservoir available to the intraerythrocytic plasmodium. Haemoglobin, ingested via the cytostome, is held in food vacuoles where auto-oxidation takes place. As a consequence, haem is released and accumulates in the vacuole as particulate haemozoin (= malaria pigment). Current evidence favours the view that haemozoin is mainly haematin. Acid and alkaline proteases (identified in crude extracts from mammalian and avian malarias) are presumably secreted directly into the food vacuole. They then digest the denatured globin and the resulting amino acids are incorporated into parasite protein. Cell-free protein synthesizing systems have been developed using P. knowlesi and P. lophurae ribosomes. In the main these systems are typically eukaryotic.Studies of amino acid metabolism are exceedingly limited. Arginine, lysine, methionine, and proline are incorporated into protein, whereas glutamic acid is metabolized via an NADP-specific glutamic dehydrogenase. Glutamate oxidation generates NADPH and auxiliary energy (in the form of alpha-ketoglutarate). The role of red cell glutathione in the economy of the parasite remains obscure. Important goals for future research should be: quantitative assessment of the relative importance of amino acid sources for parasite protein synthesis; purification and characterization of plasmodial proteinases; and in vitro translation of parasite messenger RNA.
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PMID:Amino acid metabolism and protein synthesis in malarial parasites. 33 83

Aflatoxin-albumin adduct levels were measured in serum samples obtained from a group of Gambian children. The relationships between exposure to aflatoxin and the prevalence of malaria, between exposure and humoral and cellular responses in vitro to defined malaria antigens and, amongst children with evidence of exposure to hepatitis B infection, between aflatoxin and carriage of the hepatitis B surface antigen (HBsAg), were assessed. Aflatoxin-albumin adduct was found in nearly all serum samples collected during a survey performed at the end of the dry season and levels of adduct were generally high (up to 720 pg aflatoxin-lysine equivalent/mg albumin). Higher levels of aflatoxin-albumin adduct were detected in Wollof children than in children of other ethnic groups and marked variation in mean adduct levels between villages was observed. Aflatoxin-albumin adduct levels were higher in children who were HbsAg positive and in children with Plasmodium falciparum parasitaemia than in controls. However, levels of adduct had no consistent effect on either malaria-specific antibody responses, lymphoproliferative responses in vitro, or morbidity from malaria during the subsequent rainy season. Much lower levels of aflatoxin-albumin adduct were detected in repeat samples obtained at the end of the rainy season. There was poor correlation between dry and rainy season levels of adduct in individual children. We have shown that Gambian children are exposed to high levels of aflatoxin. The seasonal variation of aflatoxin-albumin adduct and marked fluctuation of adduct with time in individual children need to be considered in the future planning of epidemiological studies using this marker of exposure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Aflatoxin exposure, malaria and hepatitis B infection in rural Gambian children. 144 Aug 26

The KEK (Lysine-Glutamic acid-Lysine) motif is frequently found in the primary structure of certain malaria proteins involved in invasion, and plays an important role in the interaction of these proteins with the erythrocyte. This motif is contained in a peptide which forms part of the polymeric synthetic malaria vaccine SPf 66, currently undergoing extensive human trials. Analysis of the antibody titres against the subunit peptides that comprise this vaccine has shown that protection is associated with high titres to the KEK-containing peptide. In this paper we examine the fine recognition of this motif by polyclonal sera from protected vaccinated individuals, demonstrating the critical role played by the interacting ion pair formed between the amino terminal lysine (K) and glutamic acid (E), which act as contact residues for an important proportion of the antibody population directed against this vaccine. This ion pair in the KEK motif constitutes perhaps one of the most important malaria epitopes involved in protection, and could explain the mechanism through which protective immunity is acquired.
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PMID:In human malaria protective antibodies are directed mainly against the Lys-Glu ion pair within the Lys-Glu-Lys motif of the synthetic vaccine SPf 66. 155 26

The C-terminal domain (CTD) of RNA polymerase II (RNAP) has an essential function in the regulation of transcription. The CTD of the human malaria parasite, Plasmodium falciparum, differs dramatically from that of higher eukaryotes. To determine whether this is a general feature of malarial parasites, we have analysed the CTD of the distantly related rodent malaria parasite P.berghei. The CTDs of the two parasites enzymes are very similar in amino acid composition and contain the basic structure of most eukaryotic CTDs, which is a tandem repeat of a heptapeptide (SPTSPSY). The CTD of P.berghei differs, however, in three aspects from the CTD of P.falciparum and other eukaryotes. First, both domains show a divergence from the consensus sequence at position 6 of the heptapeptide repeat. The Ser6 is always substituted, with a bias for lysine. The latter substitution might increase the binding efficiency to the DNA template. Second, the rodent and human malarial CTDs contain a 3' extension of, respectively, 66 or 67 amino acid residues. This tail-piece is unique among eukaryotes. Third, the enlargement of the CTD of the human parasite by six heptapeptide repeats is most likely generated by a recent amplification of a specific repeat unit.
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PMID:The C-terminal domain of RNA polymerase II of the malaria parasite Plasmodium berghei. 184 Apr 89

The major repetitive epitopes of the surface circumsporozoite (CS) protein of malaria sporozoites represent candidates for the development of subunit vaccines against malaria. However, previous experimental work has shown that repetitive peptides from the CS proteins of Plasmodium falciparum, P. vivax, P. yoelii and P. berghei are immunogenic only in mice with the H-2b or H-2k haplotype. This led to the conclusion that strong T helper epitopes from the non-repetitive CS sequences were required in the design of sporozoite vaccines. In the present study, we investigated the immunogenicity in mice of a octa-branched multiple antigen peptide (MAP) containing repeats of the CS protein of the human malaria parasite, P. malariae, [MAP8(NAAG)6], and found that mice with an H-2b, H-2d, H-2k, H-2f, H-2q, and H-2s haplotype produced anti-peptide antibodies after immunization and that only H-2r mice were nonresponsive. This antibody response, not induced in athymic H-2b nu/nu mice, was directed against the (NAAG) sequence, but not against the lysine core of the MAP construct. Finally, when covalently linked to a synthetic polymer of the repetitive (NANP) sequence of the P. falciparum CS protein, [MAP8(NAAG)6] behaved as a carrier molecule for the production of anti-(NANP)n antibodies in H-2d and H-2k mice, genetically nonresponder to the (NANP)n sequence. Should this wide immunogenicity of the P. malariae CS (NAAG) repetitive sequence also apply to humans, it might be considered for the design of multivalent subunit malaria vaccines.
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PMID:A multiple antigen peptide from the repetitive sequence of the Plasmodium malariae circumsporozoite protein induces a specific antibody response in mice of various H-2 haplotypes. 220 49

The transbilayer distribution of glycerophospholipids in the plasma membrane of Plasmodium knowlesi infected erythrocytes was studied by using lysine-116-epsilon-N-palmitoyl amidinated pancreatic phospholipase A2. As a consequence of its superior membrane penetrating capacities, this modified enzyme rapidly degrades its substrates in the outer membrane leaflet of intact erythrocytes, a property that makes the enzyme an excellent tool to study the malaria parasitized red cell. The modified phospholipase A2 caused a nonlytic hydrolysis of up to 12-15% of the phosphatidylethanolamine and none of the phosphatidylserine in the red cell membrane, irrespective of whether the cells harboured trophozoite and schizont stages of parasites or no parasites at all. The absence of phosphatidylserine at the exterior surface of Plasmodium infected erythrocytes was confirmed by applying the prothrombinase assay on Plasmodium falciparum infected human erythrocytes. Consequently, the results from these and previous studies indicate that the plasma membrane of Plasmodium infected erythrocytes exhibit a normal transbilayer phospholipid asymmetry.
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PMID:Phospholipid asymmetry in the plasma membrane of malaria infected erythrocytes. 234 3

A relationship was found between resistance of malarial plasmodium to chloroquine and the increased activity of microsomal monooxygenases, metabolizing drugs in the parasite. A search for effective inhibitors of the enzymatic system was initiated. For this purpose inhibitory effects of 17 alpha-hydrodeoxycorticosterone (substance S), 21-acetate-17 alpha-hydroxydeoxycorticosterone (acetate of substance S), 4-bromomethyl-2,2,5,5-tetramethyl-3-imidazoline-3-oxide-1-oxyl (RBr), Cu(lysine)2 on activity of arylhydroxycarbone hydroxylase were studied using mice liver microsomes and homogenate of mice malaria cells Plasmodium berghei. Cu(lysine)2 and phenylhydrazine were found to be the most effective inhibitors of the enzyme in samples containing mice liver microsomes or malarial parasite. The data obtained suggest that the inhibitors of microsomal monooxygenases may serve as means for a decrease in malarial parasite resistance to chloroquine.
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PMID:[Microsomal monooxygenase inhibitors as promising agents for overcoming the drug resistance of the malaria parasite]. 391 72

The effect of protease inhibitors on invasion of rhesus erythrocytes by Plasmodium knowlesi merozoites was evaluated. Chymostatin, N-alpha-p-tosyl-L-lysine chloromethyl ketone (TLCK), and L-1-tosylamide-2-phenylethylchloromethyl ketone (TPCK) inhibited invasion. Leupeptin, antipain, pepstatin, and phenylmethylsulfonyl fluoride (PMSF) had no effect. TLCK and TPCK inhibited attachment of merozoites to host erythrocytes. Chymostatin had no adverse effect on attachment, and in its presence junction formation between the merozoite and host erythrocyte occurred. Both chymostatin and leupeptin inhibited normal rupture of schizont-infected erythrocytes. It is suggested that proteolytic activity may be important both in the rupture of schizont-infected erythrocytes and in the invasion of erythrocytes by malaria parasites.
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PMID:Plasmodium knowlesi: studies on invasion of rhesus erythrocytes by merozoites in the presence of protease inhibitors. 685 69

In this report we describe a novel gene delivery system using malaria circumsporozoite (CS) protein as a specific ligand. The CS protein covers the entire surface of sporozoites of malaria parasites. Previous studies have demonstrated that intravenously injected CS protein binds specifically to the basolateral surface of hepatocytes within minutes, indicating the high hepatocyte specificity of CS protein. This characteristic of CS protein prompted us to explore the possibility of using this protein as a liver-specific ligand for hepatic gene delivery vehicle. As an initial step, we investigated the efficacy of CS protein-mediated gene transfer into primary hepatocytes as well as established cell lines. Recombinant CS proteins were chemically conjugated to poly(L-lysine). The CS conjugates were complexed with recombinant plasmid DNA carrying a reporter gene. When the DNA complex was used to transfect primary hepatocytes, a very low level of expression of the reporter gene was observed. The level of expression was greatly enhanced when the cells were cotransfected with adenovirus, which presumably releases the internalized DNA from endosomal entrapment. The CS-mediated gene transfer into the cells required region II+, an evolutionarily conserved amino acid sequence conferring the binding of CS protein to its receptor. CS protein also efficiently mediated gene transfer into a number of cell lines, i.e. HepG2, HeLa, NIH3T3, and K562, but not HL-60, which contains low levels of receptor. Thus, the CS conjugate can be used to deliver DNA into many different cultured cells. Most importantly, the CS conjugate has a potential to be further developed into a liver-specific gene delivery vehicle in vivo.
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PMID:Malarial circumsporozoite protein is a novel gene delivery vehicle to primary hepatocyte cultures and cultured cells. 753 54

During its 48-hour cycle inside the red blood cell, the human malaria parasite, Plasmodium falciparum, increases its volume 25-fold and divides asexually. This rapid growth demands large amounts of nutrients, a problem exacerbated by the lower metabolic rate and relative ionic impermeability of the host red blood cell. Direct passage of small nutrients across the two membranes that separate the parasite from the erythrocyte cytosol may be important for parasite development and has been demonstrated for radiolabelled glucose, amino acids, and purine nucleosides. Flux studies on plasmodia are limited, however, to suspensions of erythrocyte-free parasites and so cannot be used to examine the individual transport properties of the two membranes involved. Here we use the cell-attached patch clamp method to overcome this limitation. After removing the intervening red blood cell membrane and forming gigaohm seals on the small (3-5 microns) parasite, we studied transport across the parasitophorous vacuole membrane (PVM), the outer of the two membranes that separate the parasite from the erythrocyte cytosol. A 140-pS channel which is permeable to both cations and anions was identified on the PVM. This channel is present at high density, is open more than 98 per cent of the time at the resting potential of the PVM, and is permeable to lysine and glucuronate. The channel can readily transport amino acids and monosaccharides across the PVM and may be essential for fulfilling the parasite's metabolic demands.
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PMID:A nutrient-permeable channel on the intraerythrocytic malaria parasite. 768 37


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