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)

Bloodmeals of exophilic anopheline mosquitoes collected resting on vegetation in a malaria endemic area in western Venezuela were identified by ELISA. Using a TMB peroxidase substrate in the ELISA, human bloodmeals were readily identified up to 40 h after ingestion in all laboratory-fed mosquitoes tested. Assay sensitivity declined to 75% identifiable 44 h post-feeding. The Human Blood Index and the Feeding Index of each species differed between the three villages studied. An.triannulatus was generally more anthropophilic than An.nuneztovari and An.oswaldoi. These contrasting results emphasize the difficulties of interpreting host choice data.
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PMID:Host choice of anopheline mosquitoes in a malaria endemic area of western Venezuela. 794 19

An IgM monoclonal antibody (7C5B71) which reacted with the blood stages of Plasmodium vivax, but not with those of Plasmodium falciparum was used in a cell-ELISA to detect parasites in samples of peripheral blood. Blood thin smears were probed with monoclonal antibody 7C5B71 and then reacted with a peroxidase conjugate of the appropriate specificity and the insoluble chromogen amino-ethyl-carbazole. Infected cells which appeared dark red coloured were rapidly identified under a light microscope using a low magnification. The conventional microscopic examination of thin films coloured with Giemsa was used as reference test. Under laboratory conditions the test showed a positive result in samples with a level of parasitaemia of < or = 500 parasites/microliter of blood. In a preliminary field trial the test showed 100 % specificity for the diagnosis of P. vivax malaria.
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PMID:Sensitive detection of Plasmodium vivax in blood by a cell-ELISA using a monoclonal antibody. 874 85

We examined the optic nerve, as an analogous tissue to brain white matter, to assess possible relationships between changes in the blood-nerve barrier, axonal integrity, and astrocyte morphology in the central nervous system during fatal murine cerebral malaria (FMCM). In the FMCM model, namely, CBA mice infected with Plasmodium berghei ANKA, neurological symptoms begin around day 5 post-inoculation (p.i.) and mice become increasingly ill by day 7 p.i., at which time they lapse into coma and die. Using intravascular perfusion with horseradish peroxidase combined with light and electron microscopy, and GFAP immunohistochemistry, the optic nerves in malaria-infected mice were found to display i) breakdown of the blood-nerve barrier, detectable as early as day 3 p.i. (about 2 days before the onset of neurological symptoms) increasing to peak severity by day 7 p.i.; ii) monocytosis, vascular congestion, and monocyte adherence to the endothelium in the microvasculature during the later stages of the disease process; iii) an increased incidence of patchy axonal demyelination and degeneration, mostly associated with vascular changes and astrogliosis, beginning at day 5 p.i. and more evident by day 7 p.i.; and iv) an increased intensity of GFAP immunostaining, detectable from day 3 p.i. and peaking at day 7 p.i. These optic nerve changes were always seen in the infected individuals, though they varied in intensity. The temporal and anatomical coincidence between the compromised blood-nerve barrier, monocyte adherence to the vascular endothelium, astrocyte changes, neuronal degeneration, and demyelination in the optic nerve in FMCM suggests that these factors are mechanistically inter-related. These findings are consistent with the proposed immunopathological nature of FMCM and provide further evidence for the pivotal role of the CNS microvasculature in the disease process. This is the first investigation of involvement of the optic nerve in FMCM and the first demonstration, to our knowledge, of loss of axonal viability in this condition in any CNS tissue. The observed demyelination is consistent with reports by other workers on such changes in the brain in human cerebral malaria.
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PMID:Compromised blood-nerve barrier, astrogliosis, and myelin disruption in optic nerves during fatal murine cerebral malaria. 903 30

Insect class I glutathione S-transferases (GSTs) were expressed from cDNA obtained from larvae of the Thai malaria vector. Anopheles dirus in a PCR RACE (rapid amplification of cDNA ends) reaction using a primer to the conserved N-terminal region of An. gambiae class I GSTs and a synthetic oligo d(T)-adaptor primer. Seven different plasmids, resulting from sub-cloning of an original single 0.7 Kb PCR band, were picked at random and sequenced. Four of these were clearly GSTs on the basis of putative amino acid sequence conservation. All the sequences had a conserved N-terminal region, but were highly divergent at the C-terminus. The variability in the PCR products suggests that there is a high level of GST class I isoenzyme variability in larval An. dirus. One of the subclones from the PCR reaction contained a full coding region of the cDNA for GST. This had a putative amino acid sequence which was 76 and 91% identity to the An. gambiae GST class I, agGST 1-5 and agGST 1-6 respectively, but only 48% identity to agGST 1-2. The catalytically active enzyme, expressed in Escherichia coli, was strongly immuno-cross reactive with antisera raised against the two An. gambiae class I GSTs. The expressed enzyme was purified to homogeneity from an E. coli cell lysate by S-hexylglutathione agarose affinity chromatography. The enzyme had a high specific activity with CDNB, and also used DCNB and ethacrynic acid as substrates. In addition, it had peroxidase and DDTase activity and its activity with CDNB, was strongly inhibited by a range of organophosphorus and pyrethroid insecticides. This is consistent with the predicted role of this GST class in insecticide resistance.
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PMID:Cloning, expression and characterization of an insect class I glutathione S-transferase from Anopheles dirus species B. 969 35

We have identified the 2-Cys peroxiredoxin (PfPrx-1) from the human malaria parasite Plasmodium falciparum. The PfPrx-1 showed the highest identity at amino acid level to the type II Prx among the currently known six subfamilies of mammalian Prx. The sequence identity between the PfPrx-1 and the previously reported 1-Cys Prx of P. falciparum (PfPrx-2), which corresponded to mammalian type VI Prx, was 25%. This suggests that the parasite possesses two Prx subfamilies. The PfPrx-1 showed significant sequence similarities with those of 2-Cys peroxiredoxins of plants in the BLASTX search. This may reflect the consequences of a genetic transfer from an algal endosymbiont to the parasite nucleus during evolution. The recombinant PfPrx-1 protein (rPfPrx-1) was expressed as a histidine fusion protein in Escherichia coli and purified with Ni chromatography. The rPfPrx-1 existed as dimers under non-reducing conditions and dissociated into monomers in the presence of dithiothreitol. The PfPrx-1 protein also exists as a dimer in the parasites themselves. The reduction of the oxidized enzyme by the donation of electrons from E. coli thioredoxin (Trx)/Trx reductase system was demonstrated in its reaction with H(2)O(2), using the rPfPrx-1 protein. These results suggested that the PfPrx-1 can act as a terminal peroxidase of the parasite Trx system. An elevated expression of the PfPrx-1 protein seen in the trophozoite, the stage with active metabolism, suggests an association of the parasite Trx system with its intracellular redox control.
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PMID:Molecular characterization of a 2-Cys peroxiredoxin from the human malaria parasite Plasmodium falciparum. 1146 68

A cluster of eight genes encoding glutathione transferases (GSTs) are located on division 33B of polytene chromosome arm 3R of the African malaria mosquito, Anopheles gambiae. This region of the genome contains a major 1,1,1-trichloro-2,2-bis-( p -chlorophenyl)ethane (DDT)-resistance locus, rtd1. These GSTs belong to the insect-specific Epsilon class and share between 22.6 and 65.2% identity at the amino acid level. Two distinct allelic variants of the Epsilon GST, GSTe1, differing at 12 out of 224 amino acid residues, are present in laboratory and field populations of A. gambiae. To investigate the possible role of these GSTs in conferring resistance to the insecticide DDT, both GSTe1 alleles, plus three additional members of this gene cluster, were expressed in Escherichia coli and the recombinant proteins biochemically characterized. The five putative glutathione transferases encoded catalytically active subunits with variable biochemical properties. For example, the two allelic variants of GSTE1-1 encoded proteins with over 100-fold variation in peroxidase activity, while the three remaining GSTs had no detectable peroxidase activity. Only GSTE2-2 was able to metabolize DDT. Western blots using antibodies raised against these GSTs indicated that the expression of GSTE2-2 is elevated in a DDT-resistant strain of A. gambiae.
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PMID:Heterologous expression of four glutathione transferase genes genetically linked to a major insecticide-resistance locus from the malaria vector Anopheles gambiae. 1271 42

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

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


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