Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have earlier indicated neutrophil activation in severe malaria by measuring myeloperoxidase (MPO) and lysozyme, leukocyte granule proteins secreted by neutrophils as well as by other blood cells (monocytes/macrophages). In this study we evaluated the plasma levels of human neutrophil lipocalin (HNL), a specific neutrophil granule protein, in relation to previously reported markers MPO and lysozyme, for clinical significance in indicating severe malaria. For this purpose, plasma samples were analyzed from 65 individuals with severe malaria, mild malaria or malaria negative, all living in the Gedarif area of Sudan. The plasma levels of HNL were significantly higher in the group of patients with severe malaria as compared with the other two groups. Plasma levels of HNL correlated significantly to those of MPO and lysozyme, as well as to body temperature, degree of parasitaemia and pulse rate. These results confirm our previous findings that neutrophils are activated in-patients with severe malaria and the level of HNL is a good marker in this context.
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PMID:Human neutrophil lipocalin: a specific marker for neutrophil activation in severe Plasmodium falciparum malaria. 1282 3

Patterns of expression of the 2-Cys and 1-Cys peroxiredoxin (Prx) proteins of the rodent malaria parasite Plasmodium yoelii during its life cycle were observed by immunofluorescent antibody staining and confocal laser scanning microscopy. 2-Cys Prx was expressed in the parasite cytoplasm throughout the life cycle, and the thioredoxin (Trx)-peroxidase activity of 2-Cys Prx revealed with the recombinant protein suggested that the Prx is constitutively expressed and, thus, likely plays a housekeeping role in the parasite's intracellular redox control. In contrast, 1-Cys Prx showed stage-specific expression in blood-stage parasites. The limited expression of 1-Cys Prx in the trophozoite cytoplasm suggests that 1-Cys Prx may be involved in haemoglobin metabolism by the parasite, which generates a prooxidative haem iron and increases intracellular oxidative stress. The antioxidant activity of 1-Cys Prx was tested for its ability to protect yeast enolase against inactivation of the mixed-function oxidation system. Differential expression of the two Prx proteins during the erythrocytic and insect stages suggests the importance of these proteins in protecting parasites against oxidative stress, which is generated by the parasite's metabolism and also from the environment.
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PMID:Expression profiles of peroxiredoxin proteins of the rodent malaria parasite Plasmodium yoelii. 1457 8

Various autoantibodies like anti-nuclear antibodies (ANA), anti-double stranded DNA (anti-dsDNA), anti-histone antibodies (AHA), anti-neutrophil cytoplasmic antibodies (ANCA), anti-myeloperoxidase (anti-MPO), anti-proteinase3 (anti-PR3) and anti-lactoferrin (anti-LF) antibodies were studied in 173 acute hospitalised patients suffering from malaria of which 160 patients had P. falciparum and remaining 13 had P. vivax infection. Standard methods like indirect immunofluorescence (IIF) microscopy along with Confocal microscopy and ELISA were used for identifying and quantifying the autoantibodies and IIF patterns on PMN and HL-60 cells were studied for ANCA classification. Also HEp-2 cells were used for ANA detection, while estimation of anti-dsDNA, AHA, anti-MPO, anti-PR3 and anti-LF were tested using ELISA. Sera from malaria patients showed prominent immunofluorescence staining patterns where 23.8% cases had ANA in P. falciparum group as compared to 15.4% in P. vivax group and ANCA was found to be present in 20% in P. falciparum and 15.4% in P. vivax group. An interesting observation was that, of the total ANCA positives, 59% had p-ANCA, 5.9% had c-ANCA and 44.1% of the cases showed the 'atypical' or X-ANCA pattern. When p-ANCA positivity was compared with c-ANCA positivity among these patients, a good statistical correlation was noted with OR = 16, chi 2 = 16.43, EF = 0.46 and p-value = 5.037E 0.5. ELISA showed 31.2% anti-MPO and 6.2% anti-PR3 in P. falciparum cases while the two ANCA positive cases in P. vivax had anti-MPO. Anti-LF was found to be present in 40.6% cases. Neither the P. falciparum nor P. vivax contained autoantibodies with specificities similar to the characteristic lupus autoantibodies such as double stranded DNA (dsDNA). ANCA positivity develops in some types of malarial infection also with the presence of various autoantibodies which is important from a clinical point of view and should be carefully evaluated in those geographic areas where malaria is endemic. It also alerts us to the fact, whether in cases of repeated malarial infections in susceptible individuals, vasculitic disorders, which through ANCA pathways develop, could lead to renal and other complications.
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PMID:Anti-neutrophil cytoplasmic antibodies (ANCA) in malaria. 1468 12

Plasmodium berghei invasion of Anopheles stephensi midgut cells causes severe damage, induces expression of nitric-oxide synthase, and leads to apoptosis. The present study indicates that invasion results in tyrosine nitration, catalyzed as a two-step reaction in which nitric-oxide synthase induction is followed by increased peroxidase activity. Ookinete invasion induced localized expression of peroxidase enzymes, which catalyzed protein nitration in vitro in the presence of nitrite and H(2)O(2). Histochemical stainings revealed that when a parasite migrates laterally and invades more than one cell, the pattern of induced peroxidase activity is similar to that observed for tyrosine nitration. In Anopheles gambiae, ookinete invasion elicited similar responses; it induced expression of 5 of the 16 peroxidase genes predicted by the genome sequence and decreased mRNA levels of one of them. One of these inducible peroxidases has a C-terminal oxidase domain homologous to the catalytic moiety of phagocyte NADPH oxidase and could provide high local levels of superoxide anion (O(2)), that when dismutated would generate the local increase in H(2)O(2) required for nitration. Chemically induced apoptosis of midgut cells also activated expression of four ookinete-induced peroxidase genes, suggesting their involvement in general apoptotic responses. The two-step nitration reaction provides a mechanism to precisely localize and circumscribe the toxic products generated by defense reactions involving nitration. The present study furthers our understanding of the biochemistry of midgut defense reactions to parasite invasion and how these may influence the efficiency of malaria transmission by anopheline mosquitoes.
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PMID:Inducible peroxidases mediate nitration of anopheles midgut cells undergoing apoptosis in response to Plasmodium invasion. 1545 81

Metabolic pathways play an important role in insecticide resistance, but the full spectra of the genes involved in resistance has not been established. We constructed a microarray containing unique fragments from 230 Anopheles gambiae genes putatively involved in insecticide metabolism [cytochrome P450s (P450s), GSTs, and carboxylesterases and redox genes, partners of the P450 oxidative metabolic complex, and various controls]. We used this detox chip to monitor the expression of the detoxifying genes in insecticide resistant and susceptible An. gambiae laboratory strains. Five genes were strongly up-regulated in the dichlorodiphenyltrichloroethane-resistant strain ZAN/U. These genes included the GST GSTE2, which has previously been implicated in dichlorodiphenyltrichloroethane resistance, two P450s, and two peroxidase genes. GSTE2 was also elevated in the pyrethroid-resistant RSP strain. In addition, the P450 CYP325A3, belonging to a class not previously associated with insecticide resistance, was expressed at statistically higher levels in this strain. The applications of this detox chip and its potential contribution to malaria vector insecticide resistance management programs are discussed.
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PMID:The Anopheles gambiae detoxification chip: a highly specific microarray to study metabolic-based insecticide resistance in malaria vectors. 1575 17

A peroxidase (30 kDa) has been purified from the human malaria parasite Plasmodium falciparum to its homogeneity. The protein is a dimer of 15 kDa subunit as evident from SDS-PAGE and MALDI-TOF mass analysis. The antibodies developed against the purified protein cross-react selectively with this protein present in parasite lysate. It is a heme containing peroxidase [R/Z value (A408/A278)=2.33] showing characteristic heme spectra with Soret peak at 408 nm and visible peaks at 536 and 572 nm. Analysis of Soret spectra in presence or absence of cyanide or azide reveals that iron of heme is in Fe-III state. Circular dichroism spectral analysis establishes that this protein contains mainly alpha-helix (60-70%). H2O2 interacts with the heme moiety of the enzyme as evidenced by optical difference spectroscopy and spectral studies indicate the formation of catalytically active peroxidase-H2O2 complex (Soret peak at 413 nm) to exhibit peroxidase activity. During the erythrocytic stages of its life cycle, the parasite is exposed to oxidative stress. As the parasite is susceptible to oxidative stress, this peroxidase may offer antioxidant role by scavenging endogenous H2O2.
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PMID:Purification and biochemical characterization of a heme containing peroxidase from the human parasite P. falciparum. 1580 33

Malarial pigment, a unique hemozoin crystal composed of unit cells of heme dimers, is present in large amounts in circulating monocytes and neutrophils and can persist unchanged in macrophages for several months. In the present study, we investigated the effect of hemozoin not only on macrophages, but also on neutrophils. We used beta-hematin (BH), a chemically synthetic crystal structurally identical to hemozoin, for these studies. In vitro, BH up-regulated the expression of tumor necrosis factor-alpha in whole blood and in isolated peritoneal macrophages, indicating that hemozoin is able to stimulate monocytes. BH stimulated murine peritoneal neutrophils to express macrophage inflammatory protein-2 (MIP-2), a homologue of human interleukin-8 that is used as a marker of neutrophil activation. Injecting BH into the peritoneal cavity resulted in a dose-dependent migration of neutrophils and a high level of myeloperoxidase activity of peritoneal cells. Finally, BH directly induced neutrophil chemotaxis in vitro. Taken together, these results suggest that the malarial pigment hemozoin can activate leukocytes and may participate in the pathology of severe malaria.
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PMID:Leukocyte activation by malarial pigment. 1631 76

Malaria parasite glutathione S-transferases (GSTs) are postulated to be essential for parasite survival by protecting the parasite against oxidative stress and buffering the detoxification of heme-binding compounds; therefore, GSTs are considered potential targets for drug development. In this study, we identified a Plasmodium vivax gene encoding GST (PvGST) and characterized the biochemical properties of the recombinant enzyme. The PvGST contained 618 bp that encoded 205 amino acids and shared a significant degree of sequence identity with GSTs from other Plasmodium species. The recombinant homodimeric enzyme had an approximate molecular mass of 50kDa and exhibited GSH-conjugating and GSH-peroxidase activities towards various model substrates. The optimal pH for recombinant PvGST (rPvGST) activity was pH 8.0, and the enzyme was moderately unstable at 37 degrees C. The K(m) values of rPvGST with respect to GSH and CDNB were 0.17+/-0.09 and 2.1+/-0.4mM, respectively. The significant sequence homology and similar biochemical properties of PvGST and Plasmodium falciparum GST (PfGST) indicate that they may have similar molecular structures. This information may be useful for the design of specific inhibitors for plasmodial GSTs as potential antimalarial drugs.
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PMID:Plasmodium vivax: molecular cloning, expression and characterization of glutathione S-transferase. 1745 79

The intra-erythrocytic stages of the malaria parasite endocytose large quantities of the surrounding erythrocyte cytoplasm and deliver it to a digestive food vacuole via endocytic vesicles. Digestion provides amino acids for parasite protein synthesis and is required to maintain the osmotic integrity of the host cell. The parasite endocytic pathway has been described morphologically by electron microscopy, but the molecular mechanisms that mediate and regulate it remain elusive. Given the involvement of actin in endocytosis in other eukaryotes, we have used actin inhibitors to assess the requirement for this protein in the endocytic pathway of the human malaria parasite, Plasmodium falciparum. Treatment of cultures with cytochalasin D did not affect haemoglobin levels in the parasites when co-administered with protease inhibitors, and neither did it affect the uptake of the endocytic tracer horseradish peroxidase, suggesting the absence of actin in the mechanism of endocytosis. However, in the absence of protease inhibitors, treated parasites contained increased levels of haemoglobin due to an accumulation of enlarged endocytic vesicles, as determined by immunofluorescence and electron microscopy, suggesting a role for actin in vesicle trafficking, possibly by mediating vesicle maturation and/or fusion to the digestive vacuole. In contrast to cytochalasin D, treatment with jasplakinolide led to an inhibition of endocytosis, an accumulation of vesicles closer to the plasma membrane and a marked concentration of actin in the parasite cortex. We propose that the stabilization of cortical actin filaments by jasplakinolide interferes with normal endocytic vesicle formation and migration from the cell periphery.
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PMID:Actin is required for endocytic trafficking in the malaria parasite Plasmodium falciparum. 1794 61

Cellular redox metabolism is considered to be involved in the pathophysiology of diseases caused by protozoal parasites such as Toxoplasma, Trypanosoma, Leishmania, and Plasmodia. Redox reactions furthermore are thought to play a major role in the action of and the resistance to some clinically used antiparasitic drugs. Interestingly, in malarial parasites, the antioxidant enzymes catalase and glutathione peroxidase are absent which indicates a crucial role of the thioredoxin system in redox control. Besides a glutathione peroxidase-like thioredoxin peroxidase and a glutathione S-transferase with slight peroxidase activity, Plasmodium falciparum (the causative agent of tropical malaria) possesses four classical peroxiredoxins: Two peroxiredoxins of the typical 2-Cys Prx class, one 1-Cys peroxiredoxin with homology to the atypical 2-Cys Prx class, and a peroxiredoxin of the 1-Cys Prx class have been identified and partially characterized In our article we give an introduction to redox-based drug development strategies against protozoal parasites and summarize the present knowledge on peroxiredoxin systems in Plasmodium.
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PMID:Peroxiredoxin systems of protozoal parasites. 1808 96


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