121 results on '"Schrével J"'
Search Results
2. Discovery of new targets for antimalarial chemotherapy
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Grellier P., Depoix D., Schrével J., and Florent I.
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antimalarials ,drug targets ,artemisinin ,SERCA ,apicoplast ,isoprenoid ,haem ,farnesyltransferase ,Infectious and parasitic diseases ,RC109-216 - Abstract
The understanding of the biology and the biochemistry of malaria parasites has considerably increased over the past two decades with the discovery of many potential targets for new antimalarial drugs. The decrypted genomes of several Plasmodium species and the new post-genomic tools further enriched our “reservoir” of targets and increased our ability to validate potential drug targets or to study the entire parasite metabolism. This review discusses targets involved in calcium metabolism, protein prenylation and apicoplast functions that have emerged by different approaches. more...
- Published
- 2008
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Catalog
3. New trends in chemotherapy on human and animal blood parasites
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Schrével, J., Millerioux, Valérie, Sinou, Véronique, Frappier, François, Santus, René, and Grellier, Philippe
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- 1996
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4. Sitamaquine
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Schrevel, J. and Loiseau, P.M.
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- 2015
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5. Synthesis and activity of pyrrolidinyl- and thiazoldinyl-dipeptide derivatives as inhibitors of the Tc80 prolyl oligopeptidase from Trypanosoma cruzi
- Author
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Joyeau, R., Maoulida, C., Guillet, C., Frappier, F., Teixeira, A.R.L., Schrével, J., Santana, J., Grellier, P., Laboratoire de chimie et biochimie des substances naturelles, and Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS) more...
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[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM] - Published
- 2000
6. Malaria, Microtubules and Merozoite Invasion
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Hommel, M., primary and Schrével, J., additional
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- 1998
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7. Interactions between docetaxel (Taxotere) and Plasmodium falciparum-infected erythrocytes.
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Schrével, J, primary, Sinou, V, additional, Grellier, P, additional, Frappier, F, additional, Guénard, D, additional, and Potier, P, additional
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- 1994
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8. Plasmodium falciparum proteinases: cloning of the putative gene coding for the merozoite proteinase for erythrocyte invasion (MPEI) and determination of hydrolysis sites of spectrin by Pf37 proteinase
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Florent, I., primary, Le Bonniec, S., additional, Carcy, B., additional, Grellier, P., additional, Mercereau-Puijalon, O., additional, Bonnefoy, S., additional, Dhermy, D., additional, Monsigny, M., additional, Mayer, R., additional, and Schrével, J., additional more...
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- 1994
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9. Characterization of a monoclonal antibody to human proacrosin and its use in acrosomal status evaluation.
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Gallo, J M, primary, Escalier, D, additional, Grellier, P, additional, Précigout, E, additional, Albert, M, additional, David, G, additional, and Schrével, J, additional
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- 1991
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10. Spectrin-based skeleton in red blood cells and malaria.
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Dhermy D, Schrével J, and Lecomte M
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- 2007
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11. Observations Biologiques et Ultrastructurales sur les Selenidiidae et Leurs Conséquences sur la Systématique des Grégarinomorphes.
- Author
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SCHRéVEL, J.
- Published
- 1971
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12. Plasmepsin II, an acidic hemoglobinase from the Plasmodium falciparum food vacuole, is active at neutral pH on the host erythrocyte membrane skeleton.
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Le Bonniec, S, Deregnaucourt, C, Redeker, V, Banerjee, R, Grellier, P, Goldberg, D E, and Schrével, J
- Abstract
Plasmepsin II, an aspartic protease from the human intraerythrocytic parasite Plasmodium falciparum, is involved in degradation of the host cell hemoglobin within the acidic food vacuole of the parasite. Previous characterization of enzymatic activities from Plasmodium soluble extracts, responsible for in vitro hydrolysis of erythrocyte spectrin, had shown that the hydrolysis process occurred at pH 5.0 and involved aspartic protease(s) cleaving mainly within the SH3 motif of the spectrin alpha-subunit. Therefore, we used a recombinant construct of the erythroid SH3 motif as substrate to investigate the involvement of plasmepsins in spectrin hydrolysis. Using specific anti-plasmepsin II antibodies in Western blotting experiments, plasmepsin II was detected in chromatographic fractions enriched in the parasite SH3 hydrolase activity. Involvement of plasmepsin II in hydrolysis was demonstrated by mass spectrometry identification of cleavage sites in the SH3 motif, upon hydrolysis by Plasmodium extract enzymatic activity, and by recombinant plasmepsin II. Furthermore, recombinant plasmepsin II digested native spectrin at pH 6.8, either purified or situated in erythrocyte ghosts. Additional degradation of actin and protein 4.1 from ghosts was observed. Specific antibodies were used in confocal imaging of schizont-infected erythrocytes to localize plasmepsin II in mature stages of the parasite development cycle; antibodies clearly labeled the periphery of the parasites. Taken together, these results strongly suggest that, in addition to hemoglobin degradation, plasmepsin II might be involved in cytoskeleton cleavage of infected erythrocytes. more...
- Published
- 1999
13. Ultrastructural visualization of cellular carbohydrate components by means of lectins on ultrathin glycol methacrylate sections.
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Gros, D, Obrénovitch, A, Challice, C E, Monsigny, M, and Schrével, J
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A method for the visualization of cellular carbohydrate components by both light and electron microscopy using lectins on glycol methacrylate sections is proposed. This method, which is an application of the lectin-peroxidase affinity technique, solves the problem of limited penetration when it is attempted to demonstrated lectins receptors within the tissue block. Following partial dissolution of glycol methacrylate from thin sections using alcohol, they are incubated successively with lectin (Concanavalin A or wheat germ agglutinin), horseradish peroxidase (Sigma, type II), 3-3' diaminobenzidine and H2O2 and then with OsO4-Different kinds of tissues and cells have been used to test the method: mouse myocardium, rat epididymis, a protozoon Gregarina blaberae and the bacterium Escherichia coli. The localization of carbohydrate residues deomonstrated by this method within the different tissues and cells is consistent with the findings from other published studies. Controls have been performed (i.e., omission of the lectin, lectin and its inhibitor) and these demonstrate the specificity of the method. more...
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- 1977
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14. The three cortical membranes of the gregarines: I. Ultrastructural organization of Gregarina blaberae
- Author
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Schrével, J., E. Caigneaux, D., Gros, D., and Philippe, M.
- Abstract
Gregarines, parasitic protozoa of invertebrates, possess a highly differentiated cell surface, with three cortical membranes and associated structures. Transmission electron microscopy and freezefracture reveal the presence of two cytomembranes lying uniformly under the plasma membrane. The density and the distribution of the intramembraneous particles (IMPs) in the plasma membrane of Gregarina blaberae are similar to those reported for other eukaryotic cells. The IMP density is lower in the cytomembranes than in the plasma membrane. The distribution of IMPs in the different fracture faces of the two cytomembranes suggests that they are in topological continuity, forming either side of a flattened vesicle or cisterna. The sizes of the cytomembrane IMPs show a high variability. The nature of the IMPs, both for the plasma membrane and the cytomembranes, is discussed with regard to the integral proteins and glycoproteins of the ghost. The cell surface of G. blaberae exhibits numerous longitudinal folds with three types of cortical membrane-associated structures: 12 nm filaments, an internal lamina, and homogeneous structures described as ‘rippled dense structures’. The 12 nm filaments, running under the cytomembranes along the longitudinal axis of each fold, exhibit the properties of intermediate filaments. Their distribution in mature cells and during the growth process suggests a participation in cell surface morphogenesis. The internal lamina, also localized under the cytomembranes, would stabilize each fold and assure a scaffolding function between the numerous folds. The rippled dense structures, settled on the external cytomembrane, show a regular distribution at the top of each fold. The membrane-associated structures are discussed with regard to the gliding movement mechanism. more...
- Published
- 1983
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15. Proacrosin as a marker of meiotic and post-meiotic germ cell differentiation: quantitative assessment of human spermatogenesis with a monoclonal antibody
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Bermúdez, D., Escalier, D., Gallo, J. M., Viellefond, A., Ríus, F., de Vargas, I. Pérez, and Schrével, J.
- Abstract
A quantitative immunohistochemical study of human spermatogenesis was performed using the 4D4 anti-proacrosin monoclonal antibody (mAb 4D4) as a marker of meiotic and post-meiotic germ cell differentiation. Cells from 15 testicular biopsies with normal spermatogenesis, 18 with slight and nine with marked hypospermatogenesis and six with maturation arrest were assigned to spermatogenic stages according to both nuclear maturation and proacrosin labelling patterns. The results showed that four spermatogenesis steps (mid- and late-pachytene primary spermatocytes, early and late spermatids) have to be separately considered for the classification of a given biopsy. Conversely, data from primary spermatocytes in the metaphase, anaphase and telophase stages and secondary spermatocytes did not show significant differences between biopsies. We conclude that: (1) slight hypospermatogenesis is due only to fewer cells entering meiosis, whereas in marked hypospermatogenesis there is also germ cell loss during the later meiotic steps and spermiogenesis; (2) the sloughing of germ cells from the epithelium could be of pathological significance; and (3) immunodetection with mAb 4D4 improves the assessment of spermatogenesis because it can label a protein expressed as early as meiotic prophase. In addition, mAb 4D4 labels a protein which is a marker of the Golgi complex allowing the detection of disturbances of cytoplasmic events during meiosis or spermiogenesis. Such an analysis is facilitated by mAb 4D4 labelling of paraffin-embedded sections. more...
- Published
- 1994
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16. The three cortical membranes of the gregarines (parasitic protozoa). Characterization of the membrane proteins of Gregarina blaberae
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Philippe, M. and Schrével, J.
- Abstract
Gregarines, which are parasitic protozoa living in invertebrates, possess a cortical structure specific to their vegetative stage: namely two additional cytomembranes are lying just under the plasma membrane. This cortical complex has been isolated by centrifugation on discontinuous sucrose gradients and characterized chemically. Its integrity was tested by electron microscopy. Ghost proteins were resolved by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. About 30 polypeptides of mol.wt. 15000–300000 were present in this fraction and four glycoproteins were detected after periodate/Schiff staining. Ten major proteins were labelled after lactoperoxidase-catalysed iodination. The GP2 glycoprotein (41000–49000 apparent mol.wt.) appears to be a major component of the cell surface. Effects of trypsin and Pronase digestion on ghosts and cells were monitored by gel electrophoresis and by electron microscopy. Ghosts treated with low trypsin or Pronase concentrations (10–25μg/ml) became drastically disorganized; many proteins were vigorously attacked in comparison with those of control ghosts. Variations in proteinase-sensitivity of proteins are pointed out. The GP3 glycoprotein (130000–160000 apparent mol.wt.) seemed to be the only glycoprotein released from the cell surface by trypsin. Whole cells treated under the same conditions or with higher proteinase concentrations (up to 1mg/ml) do not exhibit morphological modifications of the cell surface; furthermore, no discernible cleavage of membrane proteins was indicated by electrophoretograms. It is postulated that cell-surface proteins are protected by the dense carbohydrate cell coat. By using various different methods (change of ionic strength, detergent, denaturing agent, labelling experiment) it was possible to localize several major proteins within the protozoon cortical membranes. more...
- Published
- 1982
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17. Homologies between paraflagellar rod proteins from trypanosomes and euglenoids revealed by a monoclonal antibody
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Jm, Gallo and Schrével J
- Subjects
Molecular Weight ,Epitopes ,Species Specificity ,Flagella ,Crithidia ,Immunochemistry ,Trypanosoma brucei brucei ,Protozoan Proteins ,Animals ,Antibodies, Monoclonal ,Euglena gracilis ,Antigens, Protozoan - Abstract
A Nonidet P 40 insoluble fraction was isolated from Trypanosoma brucei and was used to raise a monoclonal antibody (5E9). The antigen was localized by indirect immunofluorescence in the flagellum of T. brucei and of two species of euglenoids, Euglena gracilis and Distigma proteus. In immunoblot analysis, 5E9 appeared to bind to paraflagellar rod proteins PFR1 and PFR2 of T. brucei (72000 and 75000 mol. wt.) and of E. gracilis (67000 and 76000 mol. wt.). The presence of a common epitope in paraflagellar rod proteins from species of trypanosomes and euglenoids shows that despite distinct structures of the rods some identical domain exists in the proteins that could be involved in their supramolecular assembly into a similar organelle. The antigenic determinant defined by 5E9 was also shown to be present in a 87000 molecular weight polypeptide located in the proximal part of the flagellum of Crithidia oncopelti in which a paraflagellar rod is not detectable at the ultrastructural level. more...
- Published
- 1985
18. Differential distribution of tubulin epitopes in human spermatozoa
- Author
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Jean-Marc Gallo, Escalier D, Schrével J, and David G
- Subjects
Male ,Paper ,Epitopes ,Tubulin ,Sperm Tail ,Antibodies, Monoclonal ,Collodion ,Fluorescent Antibody Technique ,Humans ,Electrophoresis, Polyacrylamide Gel ,Microtubules ,Spermatozoa - Abstract
Two monoclonal antibodies (16 D3 and 24 E3) were used to map tubulin domains in human spermatozoa by indirect immunofluorescence. Their specificity to tubulin in these cells was established by Western blotting. Whereas 16 D3 uniformly stained the principal piece of the flagellum, the staining provided by 24 E3 decreased along the tail to become very weak 30 micron further away from the midpiece. This latter antibody also reacted with the proximal centriole as well as the midpiece, but not all spermatozoa stained identically at this level indicating heterogeneity within the population of sperm cells from a given donor. 16 D3 reacted weakly with the head, and the staining was interrupted after a bright spot in the neck. The study of a pathological case (the short tail spermatozoon) with an abnormal arrangement of dense fibers was consistent with a correlation between the distribution of the epitope defined by 24 E3 and that of peri-axenomal structures. The existence of tubulin domains interacting with these structures is postulated. more...
19. Etude ultrastructurale des mitoses multiples au cours de la sporogonie du Plasmodium b. berghei
- Author
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Schrével, J., primary, Asfaux-Foucher, G., additional, and Bafort, J.M., additional
- Published
- 1977
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20. Observations Biologiques et Ultrastructurales sur les Selenidiidae et Leurs Conséquences sur la Systématique des Grégarinomorphes
- Author
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SCHRéVEL, J., primary
- Published
- 1971
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21. The storage polysaccharide (paraglycogen) of the gregarine, Gregarina blaberae: cytology and biochemistry
- Author
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Mercier, C., primary, Schrével, J., additional, and Stark, J.R., additional
- Published
- 1973
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22. Formation and growth of gap junctions in mouse myocardium during ontogenesis: Quantitative data and their implications on the development of intercellular communication
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Gros, D., Mocquard, J.P., Challice, C.E., and Schrevel, J.
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- 1979
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23. Evolution of the surface of mouse myocardial cells during ontogenesis II. Changes of fluorescent lectin-binding sites
- Author
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Gros, D., Bruce, B., Kiéda, C., Delmotte, F., Monsigny, M., and Schrével, J.
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- 1983
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24. Composition en glucides conjugués de l'hémolymphe de Blaberus craniifer: Variations au moment de l'ecdysis imaginale
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Philippe, M., Fournet, B., and Schrevel, J.
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- 1976
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25. Cytosolic Free Calcium in Plasmodium falciparum-Infected Erythrocytes and the Effect of Verapamil: A Cytofluorometric Study
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Adovelande, J., Bastide, B., Deleze, J., and Schrevel, J.
- Published
- 1993
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26. Plasmodium falciparum: Typing of Malaria Parasites Based on Polymorphism of a Novel Multigene Family
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Carcy, B., Bonnefoy, S., Schrevel, J., and Mercereaupuijalon, O.
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- 1995
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27. Babesia divergens: Characterization of a 17-kDa Merozoite Membrane Protein
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Precigout, E., Valentin, A., Carcy, B., Gorenflot, A., Nakamura, K.I., Aikawa, M., and Schrevel, J.
- Published
- 1993
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28. INFLUENCE DE LA TEMPÉRATURE SUR LA GAMOGONIE DE LECUDINA TUZETAE SCHREVEL, GREGARINE PARASITE DE NEREIS DIVERSICOLOR O. F. MULLER
- Author
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SCHREVEL, J.
- Published
- 1966
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29. L'ULTRASTRUCTURE DE LA PAROI DE QUELQUES SPOROZOAIRES, SES RAPPORTS AVEC CERTAINS ORGANITES CYTOPLASMIQUES, SON ROLE POSSIBLE DANS LA NUTRITION
- Author
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VIVIER, E., SCHREVEL, J., and HENNERÉ, E.
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- 1966
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30. Marine gregarine genomes reveal the breadth of apicomplexan diversity with a partially conserved glideosome machinery.
- Author
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Boisard J, Duvernois-Berthet E, Duval L, Schrével J, Guillou L, Labat A, Le Panse S, Prensier G, Ponger L, and Florent I
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- Animals, Crustacea genetics, Genome, Humans, Invertebrates genetics, Phylogeny, Apicomplexa genetics
- Abstract
Our current view of the evolutionary history, coding and adaptive capacities of Apicomplexa, protozoan parasites of a wide range of metazoan, is currently strongly biased toward species infecting humans, as data on early diverging apicomplexan lineages infecting invertebrates is extremely limited. Here, we characterized the genome of the marine eugregarine Porospora gigantea, intestinal parasite of Lobsters, remarkable for the macroscopic size of its vegetative feeding forms (trophozoites) and its gliding speed, the fastest so far recorded for Apicomplexa. Two highly syntenic genomes named A and B were assembled. Similar in size (~ 9 Mb) and coding capacity (~ 5300 genes), A and B genomes are 10.8% divergent at the nucleotide level, corresponding to 16-38 My in divergent time. Orthogroup analysis across 25 (proto)Apicomplexa species, including Gregarina niphandrodes, showed that A and B are highly divergent from all other known apicomplexan species, revealing an unexpected breadth of diversity. Phylogenetically these two species branch sisters to Cephaloidophoroidea, and thus expand the known crustacean gregarine superfamily. The genomes were mined for genes encoding proteins necessary for gliding, a key feature of apicomplexans parasites, currently studied through the molecular model called glideosome. Sequence analysis shows that actin-related proteins and regulatory factors are strongly conserved within apicomplexans. In contrast, the predicted protein sequences of core glideosome proteins and adhesion proteins are highly variable among apicomplexan lineages, especially in gregarines. These results confirm the importance of studying gregarines to widen our biological and evolutionary view of apicomplexan species diversity, and to deepen our understanding of the molecular bases of key functions such as gliding, well known to allow access to the intracellular parasitic lifestyle in Apicomplexa., (© 2022. The Author(s).) more...
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- 2022
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31. First Ultrastructural and Molecular Phylogenetic Evidence from the Blastogregarines, an Early Branching Lineage of Plesiomorphic Apicomplexa.
- Author
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Simdyanov TG, Paskerova GG, Valigurová A, Diakin A, Kováčiková M, Schrével J, Guillou L, Dobrovolskij AA, and Aleoshin VV
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- Apicomplexa classification, Apicomplexa ultrastructure, Basal Bodies metabolism, DNA, Protozoan genetics, Germ Cells growth & development, Germ Cells ultrastructure, Lymphocyte Activation, Microscopy, Electron, Apicomplexa genetics, Apicomplexa growth & development, Phylogeny
- Abstract
Blastogregarines are poorly studied parasites of polychaetes superficially resembling gregarines, but lacking syzygy and gametocyst stages in the life cycle. Furthermore, their permanent multinuclearity and gametogenesis by means of budding considerably distinguish them from other parasitic Apicomplexa such as coccidians and hematozoans. The affiliation of blastogregarines has been uncertain: different authors considered them highly modified gregarines, an intermediate apicomplexan lineage between gregarines and coccidians, or an isolated group of eukaryotes altogether. Here, we report the ultrastructure of two blastogregarine species, Siedleckia nematoides and Chattonaria mesnili, and provide the first molecular data on their phylogeny based on SSU, 5.8S, and LSU rDNA sequences. Morphological analysis reveals that blastogregarines possess both gregarine and coccidian features. Several traits shared with archigregarines likely represent the ancestral states of the corresponding cell structures for parasitic apicomplexans: a distinctive tegument structure and myzocytotic feeding with a well-developed apical complex. Unlike gregarines but similar to coccidians however, the nuclei of male blastogregarine gametes are associated with two kinetosomes. Molecular phylogenetic analyses reveal that blastogregarines are an independent, early diverging lineage of apicomplexans. Overall, the morphological and molecular evidence congruently suggests that blastogregarines represent a separate class of Apicomplexa., (Copyright © 2018 Elsevier GmbH. All rights reserved.) more...
- Published
- 2018
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32. Redescription and phylogenetic analyses of Durchoniella spp. (Ciliophora, Astomatida) associated with the polychaete Cirriformia tentaculata (Montagu, 1808).
- Author
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Sauvadet AL, Lynn DH, Roussel EG, Le Panse S, Bigeard E, Schrével J, and Guillou L
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- Animals, Microscopy, Electron, Transmission, Oligohymenophorea genetics, Oligohymenophorea ultrastructure, RNA, Ribosomal, 18S genetics, Oligohymenophorea classification, Oligohymenophorea physiology, Phylogeny, Polychaeta parasitology
- Abstract
Microscopic and phylogenetic analyses were performed on endocommensal astome ciliates retrieved from the middle intestine of a marine cirratulid polychaete, Cirriformia tentaculata, collected in the bay of Roscoff (English Channel, Northwest French coast) and on the Southwest English coast. Three morphotypes of the astome genus Durchoniella were identified, two corresponding to described species (the type species Durchoniella brasili (Léger and Duboscq, 1904) De Puytorac, 1954 and Durchoniella legeriduboscqui De Puytorac, 1954) while a third morphotype remains undescribed. Their small subunit (SSU) rRNA gene sequences showed at least 97.2% identity and phylogenetic analyses grouped them at the base of the subclass Scuticociliatia (Oligohymenophorea), as a sister lineage to all astomes from terrestrial oligochaete annelids. Ultrastructural examination by transmission electron microscopy and fluorescence in situ hybridization analyses revealed the presence of endocytoplasmic cocci and rod-shaped bacteria surrounded by a very thin membrane. These endocytoplasmic bacteria may play a role in the association between endocommensal astome ciliates and cirratulid polychaetes inhabiting in anoxic coastal sediments., (Copyright © 2017 Elsevier GmbH. All rights reserved.) more...
- Published
- 2017
- Full Text
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33. A new view on the morphology and phylogeny of eugregarines suggested by the evidence from the gregarine Ancora sagittata (Leuckart, 1860) Labbé, 1899 (Apicomplexa: Eugregarinida).
- Author
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Simdyanov TG, Guillou L, Diakin AY, Mikhailov KV, Schrével J, and Aleoshin VV
- Abstract
Background: Gregarines are a group of early branching Apicomplexa parasitizing invertebrate animals. Despite their wide distribution and relevance to the understanding the phylogenesis of apicomplexans, gregarines remain understudied: light microscopy data are insufficient for classification, and electron microscopy and molecular data are fragmentary and overlap only partially., Methods: Scanning and transmission electron microscopy, PCR, DNA cloning and sequencing (Sanger and NGS), molecular phylogenetic analyses using ribosomal RNA genes (18S (SSU), 5.8S, and 28S (LSU) ribosomal DNAs (rDNAs))., Results and Discussion: We present the results of an ultrastructural and molecular phylogenetic study on the marine gregarine Ancora sagittata from the polychaete Capitella capitata followed by evolutionary and taxonomic synthesis of the morphological and molecular phylogenetic evidence on eugregarines. The ultrastructure of Ancora sagittata generally corresponds to that of other eugregarines, but reveals some differences in epicytic folds (crests) and attachment apparatus to gregarines in the family Lecudinidae, where Ancora sagittata has been classified. Molecular phylogenetic trees based on SSU (18S) rDNA reveal several robust clades (superfamilies) of eugregarines, including Ancoroidea superfam. nov., which comprises two families (Ancoridae fam. nov. and Polyplicariidae) and branches separately from the Lecudinidae; thus, all representatives of Ancoroidea are here officially removed from the Lecudinidae. Analysis of sequence data also points to possible cryptic species within Ancora sagittata and the inclusion of numerous environmental sequences from anoxic habitats within the Ancoroidea. LSU (28S) rDNA phylogenies, unlike the analysis of SSU rDNA alone, recover a well-supported monophyly of the gregarines involved (eugregarines), although this conclusion is currently limited by sparse taxon sampling and the presence of fast-evolving sequences in some species. Comparative morphological analyses of gregarine teguments and attachment organelles lead us to revise their terminology. The terms "longitudinal folds" and "mucron" are restricted to archigregarines, whereas the terms "epicystic crests" and "epimerite" are proposed to describe the candidate synapomorphies of eugregarines, which, consequently, are considered as a monophyletic group. Abolishing the suborders Aseptata and Septata, incorporating neogregarines into the Eugregarinida, and treating the major molecular phylogenetic lineages of eugregarines as superfamilies appear as the best way of reconciling recent morphological and molecular evidence. Accordingly, the diagnosis of the order Eugregarinida Léger, 1900 is updated., Competing Interests: The authors declare that they have no competing interests. more...
- Published
- 2017
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34. Ultrastructure of Selenidium pendula, the Type Species of Archigregarines, and Phylogenetic Relations to Other Marine Apicomplexa.
- Author
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Schrével J, Valigurová A, Prensier G, Chambouvet A, Florent I, and Guillou L
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- Apicomplexa genetics, Apicomplexa growth & development, DNA, Protozoan genetics, DNA, Ribosomal genetics, Microscopy, Electron, Scanning, Microscopy, Electron, Transmission, Apicomplexa classification, Apicomplexa ultrastructure, Phylogeny
- Abstract
Archigregarines, an early branching lineage within Apicomplexa, are a poorly-known group of invertebrate parasites. By their phylogenetic position, archigregarines are an important lineage to understand the functional transition that occurred between free-living flagellated predators to obligatory parasites in Apicomplexa. In this study, we provide new ultrastructural data and phylogenies based on SSU rDNA sequences using the type species of archigregarines, the Selenidiidae Selenidium pendulaGiard, 1884. We describe for the first time the syzygy and early gamogony at the ultrastructural level, revealing a characteristic nuclear multiplication with centrocones, cryptomitosis, filamentous network of chromatin, a cyst wall secretion and a 9+0 flagellar axoneme of the male gamete. S. pendula belongs to a monophyletic lineage that includes several other related species, all infecting Sedentaria Polychaeta (Spionidae, Sabellaridae, Sabellidae and Cirratulidae). All of these Selenidium species exhibit similar biological characters: a cell cortex with the plasma membrane - inner membrane complex - subpellicular microtubule sets, an apical complex with the conoid, numerous rhoptries and micronemes, a myzocytosis with large food vacuoles, a nuclear multiplication during syzygy and young gamonts. Two other distantly related Selenidium-like lineages infect Terebellidae and Sipunculida, underlying the ability of archigregarines to parasite a wide range of marine hosts., (Copyright © 2016 Elsevier GmbH. All rights reserved.) more...
- Published
- 2016
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35. Synthesis of New 4-Aminoquinolines and Evaluation of Their In Vitro Activity against Chloroquine-Sensitive and Chloroquine-Resistant Plasmodium falciparum.
- Author
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Rajapakse CS, Lisai M, Deregnaucourt C, Sinou V, Latour C, Roy D, Schrével J, and Sánchez-Delgado RA
- Subjects
- Animals, Antimalarials chemical synthesis, Antimalarials chemistry, Antimalarials pharmacokinetics, Antimalarials pharmacology, Cell Line, Humans, Rats, Chloroquine chemistry, Chloroquine pharmacokinetics, Chloroquine pharmacology, Drug Resistance drug effects, Models, Chemical, Plasmodium falciparum metabolism
- Abstract
The efficacy of chloroquine, once the drug of choice in the fight against Plasmodium falciparum, is now severely limited due to widespread resistance. Amodiaquine is one of the most potent antimalarial 4-aminoquinolines known and remains effective against chloroquine-resistant parasites, but toxicity issues linked to a quinone-imine metabolite limit its clinical use. In search of new compounds able to retain the antimalarial activity of amodiaquine while circumventing quinone-imine metabolite toxicity, we have synthesized five 4-aminoquinolines that feature rings lacking hydroxyl groups in the side chain of the molecules and are thus incapable of generating toxic quinone-imines. The new compounds displayed high in vitro potency (low nanomolar IC50), markedly superior to chloroquine and comparable to amodiaquine, against chloroquine-sensitive and chloroquine-resistant strains of P. falciparum, accompanied by low toxicity to L6 rat fibroblasts and MRC5 human lung cells, and metabolic stability comparable or higher than that of amodiaquine. Computational studies indicate a unique mode of binding of compound 4 to heme through the HOMO located on a biphenyl moeity, which may partly explain the high antiplasmodial activity observed for this compound. more...
- Published
- 2015
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36. In vitro anti-Plasmodium falciparum properties of the full set of human secreted phospholipases A2.
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Guillaume C, Payré C, Jemel I, Jeammet L, Bezzine S, Naika GS, Bollinger J, Grellier P, Gelb MH, Schrével J, Lambeau G, and Deregnaucourt C
- Subjects
- Antimalarials metabolism, Antimalarials pharmacology, Cells, Cultured, Erythrocytes parasitology, Fatty Acids, Nonesterified, Humans, Lipoproteins blood, Phospholipases A2 genetics, Gene Expression Regulation, Enzymologic physiology, Phospholipases A2 metabolism, Phospholipases A2 pharmacology, Plasmodium falciparum drug effects
- Abstract
We have previously shown that secreted phospholipases A2 (sPLA2s) from animal venoms inhibit the in vitro development of Plasmodium falciparum, the agent of malaria. In addition, the inflammatory-type human group IIA (hGIIA) sPLA2 circulates at high levels in the serum of malaria patients. However, the role of the different human sPLA2s in host defense against P. falciparum has not been investigated. We show here that 4 out of 10 human sPLA2s, namely, hGX, hGIIF, hGIII, and hGV, exhibit potent in vitro anti-Plasmodium properties with half-maximal inhibitory concentrations (IC50s) of 2.9 ± 2.4, 10.7 ± 2.1, 16.5 ± 9.7, and 94.2 ± 41.9 nM, respectively. Other human sPLA2s, including hGIIA, are inactive. The inhibition is dependent on sPLA2 catalytic activity and primarily due to hydrolysis of plasma lipoproteins from the parasite culture. Accordingly, purified lipoproteins that have been prehydrolyzed by hGX, hGIIF, hGIII, and hGV are more toxic to P. falciparum than native lipoproteins. However, the total enzymatic activities of human sPLA2s on purified lipoproteins or plasma did not reflect their inhibitory activities on P. falciparum. For instance, hGIIF is 9-fold more toxic than hGV but releases a lower quantity of nonesterified fatty acids (NEFAs). Lipidomic analyses of released NEFAs from lipoproteins demonstrate that sPLA2s with anti-Plasmodium properties are those that release polyunsaturated fatty acids (PUFAs), with hGIIF being the most selective enzyme. NEFAs purified from lipoproteins hydrolyzed by hGIIF were more potent at inhibiting P. falciparum than those from hGV, and PUFA-enriched liposomes hydrolyzed by sPLA2s were highly toxic, demonstrating the critical role of PUFAs. The selectivity of sPLA2s toward low- and high-density (LDL and HDL, respectively) lipoproteins and their ability to directly attack parasitized erythrocytes further explain their anti-Plasmodium activity. Together, our findings indicate that 4 human sPLA2s are active against P. falciparum in vitro and pave the way to future investigations on their in vivo contribution in malaria pathophysiology., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.) more...
- Published
- 2015
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37. The enigma of eugregarine epicytic folds: where gliding motility originates?
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Valigurová A, Vaškovicová N, Musilová N, and Schrével J
- Abstract
Background: In the past decades, many studies focused on the cell motility of apicomplexan invasive stages as they represent a potential target for chemotherapeutic intervention. Gregarines (Conoidasida, Gregarinasina) are a heterogeneous group that parasitize invertebrates and urochordates, and are thought to be an early branching lineage of Apicomplexa. As characteristic of apicomplexan zoites, gregarines are covered by a complicated pellicle, consisting of the plasma membrane and the closely apposed inner membrane complex, which is associated with a number of cytoskeletal elements. The cell cortex of eugregarines, the epicyte, is more complicated than that of other apicomplexans, as it forms various superficial structures., Results: The epicyte of the eugregarines, Gregarina cuneata, G. polymorpha and G. steini, analysed in the present study is organised in longitudinal folds covering the entire cell. In mature trophozoites and gamonts, each epicytic fold exhibits similar ectoplasmic structures and is built up from the plasma membrane, inner membrane complex, 12-nm filaments, rippled dense structures and basal lamina. In addition, rib-like myonemes and an ectoplasmic network are frequently observed. Under experimental conditions, eugregarines showed varied speeds and paths of simple linear gliding. In all three species, actin and myosin were associated with the pellicle, and this actomyosin complex appeared to be restricted to the lateral parts of the epicytic folds. Treatment of living gamonts with jasplakinolide and cytochalasin D confirmed that actin actively participates in gregarine gliding. Contributions to gliding of specific subcellular components are discussed., Conclusions: Cell motility in gregarines and other apicomplexans share features in common, i.e. a three-layered pellicle, an actomyosin complex, and the polymerisation of actin during gliding. Although the general architecture and supramolecular organisation of the pellicle is not correlated with gliding rates of eugregarines, an increase in cytoplasmic mucus concentration is correlated. Furthermore, our data suggest that gregarines utilize several mechanisms of cell motility and that this is influenced by environmental conditions. more...
- Published
- 2013
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38. Glutathione reductase-catalyzed cascade of redox reactions to bioactivate potent antimalarial 1,4-naphthoquinones--a new strategy to combat malarial parasites.
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Müller T, Johann L, Jannack B, Brückner M, Lanfranchi DA, Bauer H, Sanchez C, Yardley V, Deregnaucourt C, Schrével J, Lanzer M, Schirmer RH, and Davioud-Charvet E
- Subjects
- Animals, Antimalarials chemistry, Antimalarials metabolism, Biocatalysis, Dose-Response Relationship, Drug, Glutathione Reductase chemistry, Humans, Mice, Molecular Structure, Naphthoquinones chemistry, Naphthoquinones metabolism, Oxidation-Reduction, Parasitic Sensitivity Tests, Structure-Activity Relationship, Antimalarials pharmacology, Glutathione Reductase metabolism, Naphthoquinones pharmacology, Plasmodium berghei drug effects, Plasmodium falciparum drug effects
- Abstract
Our work on targeting redox equilibria of malarial parasites propagating in red blood cells has led to the selection of six 1,4-naphthoquinones, which are active at nanomolar concentrations against the human pathogen Plasmodium falciparum in culture and against Plasmodium berghei in infected mice. With respect to safety, the compounds do not trigger hemolysis or other signs of toxicity in mice. Concerning the antimalarial mode of action, we propose that the lead benzyl naphthoquinones are initially oxidized at the benzylic chain to benzoyl naphthoquinones in a heme-catalyzed reaction within the digestive acidic vesicles of the parasite. The major putative benzoyl metabolites were then found to function as redox cyclers: (i) in their oxidized form, the benzoyl metabolites are reduced by NADPH in glutathione reductase-catalyzed reactions within the cytosols of infected red blood cells; (ii) in their reduced forms, these benzoyl metabolites can convert methemoglobin, the major nutrient of the parasite, to indigestible hemoglobin. Studies on a fluorinated suicide-substrate indicate as well that the glutathione reductase-catalyzed bioactivation of naphthoquinones is essential for the observed antimalarial activity. In conclusion, the antimalarial naphthoquinones are suggested to perturb the major redox equilibria of the targeted infected red blood cells, which might be removed by macrophages. This results in development arrest and death of the malaria parasite at the trophozoite stage. more...
- Published
- 2011
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39. Synthesis, characterization, and in vitro antimalarial and antitumor activity of new ruthenium(II) complexes of chloroquine.
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Rajapakse CS, Martínez A, Naoulou B, Jarzecki AA, Suárez L, Deregnaucourt C, Sinou V, Schrével J, Musi E, Ambrosini G, Schwartz GK, and Sánchez-Delgado RA
- Subjects
- Animals, Antimalarials chemistry, Antineoplastic Agents chemistry, Cell Line, Tumor, Cell Proliferation drug effects, Humans, Magnetic Resonance Spectroscopy, Models, Molecular, Molecular Structure, Plasmodium falciparum drug effects, Ruthenium Compounds chemistry, Spectrophotometry, Infrared, Antimalarials chemical synthesis, Antimalarials pharmacology, Antineoplastic Agents chemical synthesis, Antineoplastic Agents pharmacology, Chloroquine chemistry, Ruthenium Compounds chemical synthesis, Ruthenium Compounds pharmacology
- Abstract
The new Ru(II) chloroquine complexes [Ru(eta(6)-arene)(CQ)Cl2] (CQ = chloroquine; arene = p-cymene 1, benzene 2), [Ru(eta(6)-p-cymene)(CQ)(H2O)2][BF4]2 (3), [Ru(eta(6)-p-cymene)(CQ)(en)][PF6]2 (en = ethylenediamine) (4), and [Ru(eta(6)-p-cymene)(eta(6)-CQDP)][BF4]2 (5, CQDP = chloroquine diphosphate) have been synthesized and characterized by use of a combination of NMR and FTIR spectroscopy with DFT calculations. Each complex is formed as a single coordination isomer: In 1-4, chloroquine binds to ruthenium in the eta(1)-N mode through the quinoline nitrogen atom, whereas in 5 an unprecedented eta(6) bonding through the carbocyclic ring is observed. 1, 2, 3, and 5 are active against CQ-resistant (Dd2, K1, and W2) and CQ-sensitive (FcB1, PFB, F32, and 3D7) malaria parasites (Plasmodium falciparum); importantly, the potency of these complexes against resistant parasites is consistently higher than that of the standard drug chloroquine diphosphate. 1 and 5 also inhibit the growth of colon cancer cells, independently of the p53 status and of liposarcoma tumor cell lines with the latter showing increased sensitivity, especially to 1 (IC50 8 microM); this is significant because this type of tumor does not respond to currently employed chemotherapies. more...
- Published
- 2009
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40. Interplay between lipoproteins and bee venom phospholipase A2 in relation to their anti-Plasmodium toxicity.
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Guillaume C, Calzada C, Lagarde M, Schrével J, and Deregnaucourt C
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- Animals, Cattle, Chylomicrons metabolism, Erythrocytes drug effects, Erythrocytes metabolism, Erythrocytes parasitology, Fatty Acids, Nonesterified metabolism, Humans, Hydrolysis, In Vitro Techniques, Lipoproteins, VLDL metabolism, Lysophosphatidylcholines metabolism, Malaria, Falciparum blood, Malaria, Falciparum drug therapy, Malaria, Falciparum parasitology, Phospholipases A2, Plasmodium falciparum growth & development, Plasmodium falciparum pathogenicity, Serum Albumin, Bovine metabolism, Triglycerides metabolism, Bee Venoms pharmacology, Lipoproteins metabolism, Phospholipases A pharmacology, Plasmodium falciparum drug effects
- Abstract
We previously showed that the in vitro intraerythrocytic development of the malarial agent Plasmodium falciparum is strongly inhibited by secreted phospholipases A(2) (sPLA(2)s) from animal venoms. Inhibition is dependent on enzymatic activity and requires the presence of serum lipoproteins in the parasite culture medium. To evaluate the potential involvement of host lipoproteins and sPLA(2)s in malaria, we investigated the interactions between bee venom phospholipase A(2) (bvPLA(2)), human triglyceride-rich lipoproteins, and infected erythrocytes. Even at high enzyme concentration (100x IC(50)), bvPLA(2) binding to Plasmodium-infected or normal erythrocytes was not detected. On the contrary, tight association with lipoproteins was observed through the formation of buoyant bvPLA(2)/lipoprotein complexes. Direct involvement of the hydrolysis lipid products in toxicity was demonstrated. Arachidonic acid (C20:4), linoleic acid (C18:2), and, to a lesser extent, docosahexaenoic acid (C22:6) appeared as the main actors in toxicity. Minimal oxidation of lipoproteins enhanced toxicity of the lipolyzed particles and induced their interaction with infected or normal erythrocytes. Fresh or oxidized lipolyzed lipoproteins induced the parasite degeneration without host cell membrane disruption, ruling out a possible membranolytic action of fatty acids or peroxidation products in the death process. In conclusion, our data enlighten on the capability of secreted PLA(2)s to exert cytotoxicity via the extracellular generation of toxic lipids, and raise the question of whether such mechanisms could be at play in pathophysiological situations such as malaria. more...
- Published
- 2006
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41. Neurotoxicity and other pharmacological activities of the snake venom phospholipase A2 OS2: the N-terminal region is more important than enzymatic activity.
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Rouault M, Rash LD, Escoubas P, Boilard E, Bollinger J, Lomonte B, Maurin T, Guillaume C, Canaan S, Deregnaucourt C, Schrével J, Doglio A, Gutiérrez JM, Lazdunski M, Gelb MH, and Lambeau G
- Subjects
- Amino Acid Sequence, Animals, Chickens, Drosophila, Electrophoresis, Polyacrylamide Gel, Escherichia coli drug effects, HIV drug effects, HIV physiology, Male, Models, Molecular, Molecular Sequence Data, Phospholipases A metabolism, Phospholipases A pharmacology, Phospholipases A2, Plasmodium falciparum drug effects, Protein Conformation, Sequence Homology, Amino Acid, Virus Replication drug effects, Phospholipases A chemistry, Phospholipases A toxicity, Snake Venoms enzymology
- Abstract
Several snake venom secreted phospholipases A2 (sPLA2s) including OS2 exert a variety of pharmacological effects ranging from central neurotoxicity to anti-HIV activity by mechanisms that are not yet fully understood. To conclusively address the role of enzymatic activity and map the key structural elements of OS2 responsible for its pharmacological properties, we have prepared single point OS2 mutants at the catalytic site and large chimeras between OS2 and OS1, a homologous but nontoxic sPLA2. Most importantly, we found that the enzymatic activity of the active site mutant H48Q is 500-fold lower than that of the wild-type protein, while central neurotoxicity is only 16-fold lower, providing convincing evidence that catalytic activity is at most a minor factor that determines central neurotoxicity. The chimera approach has identified the N-terminal region (residues 1-22) of OS2, but not the central one (residues 58-89), as crucial for both enzymatic activity and pharmacological effects. The C-terminal region of OS2 (residues 102-119) was found to be critical for enzymatic activity, but not for central neurotoxicity and anti-HIV activity, allowing us to further dissociate enzymatic activity and pharmacological effects. Finally, direct binding studies with the C-terminal chimera, which poorly binds to phospholipids while it is still neurotoxic, led to the identification of a subset of brain N-type receptors which may be directly involved in central neurotoxicity. more...
- Published
- 2006
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42. Dynamic organization of microtubules and microtubule-organizing centers during the sexual phase of a parasitic protozoan, Lecudina tuzetae (Gregarine, Apicomplexa).
- Author
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Kuriyama R, Besse C, Gèze M, Omoto CK, and Schrével J
- Subjects
- Animals, Antibodies metabolism, Cell Nucleus metabolism, Cell Nucleus ultrastructure, Cell Nucleus Division, Centrosome metabolism, Centrosome ultrastructure, Cross Reactions, Diploidy, Female, Fertilization, Flagella metabolism, Flagella ultrastructure, Fluorescent Antibody Technique, Germ Cells metabolism, Germ Cells ultrastructure, Haploidy, Host-Parasite Interactions, Interphase, Life Cycle Stages, Male, Meiosis, Microscopy, Fluorescence, Microtubule-Organizing Center metabolism, Microtubules metabolism, Mitosis, Models, Biological, Spindle Apparatus metabolism, Spindle Apparatus ultrastructure, Zygote metabolism, Zygote ultrastructure, Apicomplexa growth & development, Apicomplexa physiology, Microtubule-Organizing Center ultrastructure, Microtubules ultrastructure, Polychaeta parasitology, Tubulin metabolism
- Abstract
Lecudina tuzetae is a parasitic protozoan (Gregarine, Apicomplexa) living in the intestine of a marine polychaete annelid, Nereis diversicolor. Using electron and fluorescence microscopy, we have characterized the dynamic changes in microtubule organization during the sexual phase of the life cycle. The gametocyst excreted from the host worm into seawater consists of two (one male and one female) gamonts in which cortical microtubule arrays are discernible. Each gamont undergoes multiple nuclear divisions without cytokinesis, resulting in the formation of large multinucleate haploid cells. After cellularization, approximately 1000 individual gametes are produced from each gamont within 24 h. Female gametes are spherical and contain interphase cytoplasmic microtubule arrays emanating from a gamma-tubulin-containing site. In male gametes, both interphase microtubules and a flagellum with "6 + 0" axonemal microtubules extend from the same microtubule-organizing site. At the beginning of spore formation, each zygote secretes a wall to form a sporocyst. Following meiotic and mitotic divisions, each sporocyst gives rise to eight haploid cells that ultimately differentiate into sporozoites. The ovoid shaped sporocyst is asymmetric and forms at least two distinctive microtubule arrays: spindle microtubules and microtubule bundles originating from the protruding apical end corresponding to the dehiscence pole of the sporocyst. Because antibodies raised against mammalian centrosome components, such as gamma-tubulin, pericentrin, Cep135, and mitosis-specific phosphoproteins, react strongly with the microtubule-nucleating sites of Lecudina, this protozoan is likely to share common centrosomal antigens with higher eukaryotes., (Copyright 2005 Wiley-Liss, Inc) more...
- Published
- 2005
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43. Molecular, functional and structural properties of the prolyl oligopeptidase of Trypanosoma cruzi (POP Tc80), which is required for parasite entry into mammalian cells.
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Bastos IM, Grellier P, Martins NF, Cadavid-Restrepo G, de Souza-Ault MR, Augustyns K, Teixeira AR, Schrével J, Maigret B, da Silveira JF, and Santana JM
- Subjects
- Amino Acid Sequence, Animals, Catalytic Domain, Cell Adhesion, Cell Line, Enzyme Inhibitors, Molecular Sequence Data, Prolyl Oligopeptidases, Protein Structure, Tertiary, Protozoan Proteins, Sequence Homology, Amino Acid, Serine Endopeptidases metabolism, Serine Endopeptidases chemistry, Trypanosoma cruzi enzymology
- Abstract
We have demonstrated that the 80 kDa POP Tc80 (prolyl oligopeptidase of Trypanosoma cruzi) is involved in the process of cell invasion, since specific inhibitors block parasite entry into non-phagocytic mammalian host cells. In contrast with other POPs, POP Tc80 is capable of hydrolysing large substrates, such as fibronectin and native collagen. In this study, we present the cloning of the POPTc80 gene, whose deduced amino acid sequence shares considerable identity with other members of the POP family, mainly within its C-terminal portion that forms the catalytic domain. Southern-blot analysis indicated that POPTc80 is present as a single copy in the genome of the parasite. These results are consistent with mapping of POPTc80 to a single chromosome. The active recombinant protein (rPOP Tc80) displayed kinetic properties comparable with those of the native enzyme. Novel inhibitors were assayed with rPOP Tc80, and the most efficient ones presented values of inhibition coefficient Ki < or = 1.52 nM. Infective parasites treated with these specific POP Tc80 inhibitors attached to the surface of mammalian host cells, but were incapable of infecting them. Structural modelling of POP Tc80, based on the crystallized porcine POP, suggested that POP Tc80 is composed of an alpha/beta-hydrolase domain containing the catalytic triad Ser548-Asp631-His667 and a seven-bladed beta-propeller non-catalytic domain. Docking analysis suggests that triple-helical collagen access to the catalytic site of POP Tc80 occurs in the vicinity of the interface between the two domains. more...
- Published
- 2005
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44. Labelling of four distinct trophozoite falcipains of Plasmodium falciparum by a cystatin-derived probe.
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Florent I, Lecaille F, Montagne JJ, Gauthier F, Schrével J, and Lalmanach G
- Subjects
- Animals, Cystatins analysis, Cysteine Endopeptidases analysis, Peptide Fragments analysis, Peptide Fragments metabolism, Cystatins metabolism, Cysteine Endopeptidases metabolism, Molecular Probes metabolism, Plasmodium falciparum enzymology, Plasmodium falciparum growth & development
- Abstract
Trophozoite cysteine protease (TCP) activity, isolated from Plasmodium falciparum soluble 100,000 g extracts, displayed native falcipain-1 kinetic parameters towards peptidyl substrates. The labelling of either isolated TCP or soluble 100,000 g extracts by a cystatin-derived probe (biotinyl-Leu-Val-Gly-CHN2) revealed a single band of ca. 30 kDa by SDS-PAGE, which was resolved into four spots displaying isoelectric points (pI) from 4.7 to 5.3 after two-dimensional separation. The molecular mass and pI correspond to those of falcipain-3, falcipain-2, falcipain-2' and falcipain-1, respectively. The two central spots were identified by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry as falcipain-2 and falcipain-2'. This activity-based probe represents a potential tool for profiling active falcipains in parasites. more...
- Published
- 2005
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45. Specific human antibodies do not inhibit Trypanosoma cruzi oligopeptidase B and cathepsin B, and immunoglobulin G enhances the activity of trypomastigote-secreted oligopeptidase B.
- Author
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Fernandes LC, Bastos IM, Lauria-Pires L, Rosa AC, Teixeira AR, Grellier P, Schrével J, and Santana JM
- Subjects
- Animals, Cathepsin B physiology, Chagas Disease immunology, Humans, Rabbits, Serine Endopeptidases physiology, Antibodies, Protozoan physiology, Cathepsin B immunology, Immunoglobulin G physiology, Serine Endopeptidases immunology, Trypanosoma cruzi enzymology, Trypanosoma cruzi immunology
- Abstract
Trypanosoma cruzi expresses oligopeptidase B and cathepsin B that have important functions in the interaction with mammalian host cells. In this study, we demonstrated that sera from both chagasic rabbits and humans have specific antibodies to highly purified native oligopeptidase B and cathepsin B. Levels of antibodies to cathepsin B were higher than those observed to oligopeptidase B by absorbance values recorded upon ELISA. We next showed that 90% and 30% of sera from individuals with mucocutaneous leishmaniasis have antibodies that recognize oligopeptidase B and cathepsin B as antigens, respectively. In addition, 55% and 40% of sera from kala-azar patients have antibodies to oligopeptidase B and cathepsin B, respectively. Sera from malaria patients did not recognize the proteases as antigens. Despite high levels of specific antibodies, sera from T. cruzi-infected patients did not inhibit the activities of either oligopeptidase B or cathepsin B. Furthermore, sera or IgG purified from either infected or non-infected individuals enhanced the enzymatic activity of the secreted oligopeptidase B. Oligopeptidase B secreted by trypomastigotes and cathepsin B released upon parasite lysis retain their enzymatic activities and may be associated with Chagas' disease pathogenesis by hydrolyzing host proteins and inducing host immune responses. more...
- Published
- 2005
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46. Toward a novel metal-based chemotherapy against tropical diseases. 7. Synthesis and in vitro antimalarial activity of new gold-chloroquine complexes.
- Author
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Navarro M, Vásquez F, Sánchez-Delgado RA, Pérez H, Sinou V, and Schrével J
- Subjects
- Animals, Antimalarials chemistry, Antimalarials pharmacology, Chloroquine chemistry, Chloroquine pharmacology, Drug Resistance, Gold Compounds chemistry, Gold Compounds pharmacology, Organogold Compounds, Organometallic Compounds chemistry, Organometallic Compounds pharmacology, Plasmodium falciparum drug effects, Structure-Activity Relationship, Antimalarials chemical synthesis, Chloroquine analogs & derivatives, Chloroquine chemical synthesis, Gold Compounds chemical synthesis, Organometallic Compounds chemical synthesis
- Abstract
A number of new Au(I) and Au(III) complexes of chloroquine (CQ) have been prepared, characterized, and evaluated in vitro against several strains of Plasmodium falciparum. [(CQ)Au(PPh(3))][NO(3)] (2) was synthesized by reaction of AuCl(PPh(3)) with AgNO(3) followed by treatment with CQ. Similar reactions of AuCl(PR(3)) (R = Me, Et) with KPF(6) and CQ yielded [(CQ)Au(PMe(3))][PF(6)] (3), and [(CQ)Au(PEt(3))][PF(6)] (4), respectively. KAuCl(4) reacted with CQ to produce the Au(III) complex [(CQ)(2)Au(Cl)(2)]Cl (5), which in turn formed [(CQ)Au(Cl)(SR)(Et(2)O)]Cl (6) by reaction with 1-thio-beta-d-glucose-2,3,4,6-tetraacetate (SRH). The new compounds were characterized by a combination of elemental analysis, fast atom bombardment mass spectrometry (FAB-MS), and NMR spectroscopy. All the complexes display in vitro activity against CQ-sensitive and CQ-resistant strains of Plasmodium falciparum. The highest activity for this series was obtained for complex 4, which is 5 times more active than chloroquine diphosphate (CQDP) against the CQ-resistant strain FcB1. On preincubation of noninfected red blood cells with complexes 1, 5, and 6, protection against subsequent infection was observed in some cases. No clear structure-activity correlations could be established for this series of compounds. more...
- Published
- 2004
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47. Anti-Plasmodium properties of group IA, IB, IIA and III secreted phospholipases A2 are serum-dependent.
- Author
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Guillaume C, Deregnaucourt C, Clavey V, and Schrével J
- Subjects
- Animals, Antimalarials metabolism, Antimalarials therapeutic use, Culture Media, Humans, Malaria, Falciparum drug therapy, Parasitic Sensitivity Tests, Phospholipases metabolism, Phospholipases therapeutic use, Plasmodium falciparum growth & development, Scorpions, Serum, Snake Venoms chemistry, Snakes, Antimalarials pharmacology, Phospholipases pharmacology, Plasmodium falciparum drug effects
- Abstract
Antibacterial, antiparasitidal and antiviral properties have recently been attributed to members of the secreted phospholipases A(2) (sPLA(2)s) superfamily. Seven sPLA(2)s from groups IA, IB, IIA and III, were tested here in different culture conditions for inhibition of the in vitro intraerythrocytic development of Plasmodium falciparum, the causative agent of the most severe form of human malaria. In the presence of human serum, all sPLA(2)s were inhibitory, with three out of seven exhibiting IC(50)<0.1 nM. In all cases, inhibition could be induced by enzymatic pre-treatment of the serum. By contrast, no effect was observed when parasites were grown in a semi-defined medium (AlbuMAX II) devoid of lipoproteins and containing 10 times less phospholipids than the medium with human serum, strongly suggesting that hydrolysis of serum generating toxic lipid by-products, rather than a direct interaction of the sPLA(2) with the infected erythrocyte, is a general feature of the anti-Plasmodium properties of sPLA(2)s. Furthermore, in serum, six out of the seven sPLA(2)s were toxic against both trophozoite and schizont stages of the parasite development, contrasting with the trophozoite-selective bee venom enzyme's toxicity. Deciphering the molecular mechanisms at play in the phenotypic singularity of the bee venom enzyme toxicity might offer new prospects in antimalarial fight. more...
- Published
- 2004
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48. Trypanosoma cruzi prolyl oligopeptidase Tc80 is involved in nonphagocytic mammalian cell invasion by trypomastigotes.
- Author
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Grellier P, Vendeville S, Joyeau R, Bastos IM, Drobecq H, Frappier F, Teixeira AR, Schrével J, Davioud-Charvet E, Sergheraert C, and Santana JM
- Subjects
- 3T3 Cells, Amino Acid Sequence, Animals, Cell Division, Cell Line, Dose-Response Relationship, Drug, Endocytosis, Enzyme Inhibitors pharmacology, Exocytosis, Fibronectins metabolism, HeLa Cells, Humans, Hydrolysis, Inhibitory Concentration 50, Kinetics, Lymph Nodes parasitology, Mice, Microscopy, Fluorescence, Models, Chemical, Molecular Sequence Data, Phagocytosis, Prolyl Oligopeptidases, Protein Structure, Tertiary, Protozoan Proteins, Rabbits, Serine Endopeptidases chemistry, Time Factors, Serine Endopeptidases metabolism, Serine Endopeptidases physiology, Trypanosoma cruzi enzymology, Trypanosoma cruzi pathogenicity
- Abstract
Trypanosoma cruzi is an intracellular protozoan parasite able to invade a wide variety of mammalian cells. To have access to the target organs/cells, the parasite must cross the basal laminae and the extracellular matrix (ECM). We previously characterized an 80-kDa proteinase (Tc80) secreted by the infective trypomastigotes that hydrolyzes native collagens and might be involved in infection by degrading ECM components. Here, we present evidence indicating a role for Tc80 in the invasion of nonphagocytic cells. Tc80 was classified as a member of the prolyl oligopeptidase (POP) family of serine proteases and was also found to hydrolyze fibronectin. Selective inhibitors for POP Tc80 were synthesized that blocked parasite entry into cells. Blockage occurred when trypomastigotes were preincubated with irreversible inhibitors but not after host cell preincubation, and the blockage correlated with inhibition of POP Tc80 activity in treated parasites. These data and the enzyme location inside a vesicular compartment close to the flagellar pocket, a specialized domain in endocytosis/exocytosis, strongly suggest a role for POP Tc80 in the maturation of parasite protein(s) and/or, after secretion, in a local action on parasite or host cell/ECM components required for invasion. more...
- Published
- 2001
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49. Bee venom phospholipase A2 induces stage-specific growth arrest of the intraerythrocytic Plasmodium falciparum via modifications of human serum components.
- Author
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Deregnaucourt C and Schrével J
- Subjects
- Animals, Culture Media, Humans, Phospholipases A metabolism, Phospholipases A2, Plasmodium falciparum growth & development, Bee Venoms enzymology, Blood, Erythrocytes parasitology, Phospholipases A pharmacology, Plasmodium falciparum drug effects
- Abstract
Secreted phospholipases A(2) (sPLA(2)s) from snake and insect venoms and from mammalian pancreas are structurally related enzymes that have been associated with several toxic, pathological, or physiological processes. We addressed the issue of whether toxic sPLA(2)s might exert specific effects on the Plasmodium falciparum intraerythrocytic development. We showed that both toxic and non-toxic sPLA(2)s are lethal to P. falciparum grown in vitro, with large discrepancies between respective IC(50) values; IC(50) values from toxic PLA(2)s ranged from 1.1 to 200 pm, and IC(50) values from non-toxic PLA(2)s ranged from 0.14 to 1 microm. Analysis of the molecular mechanisms responsible for cytotoxicity of bee venom PLA(2) (toxic) and hog pancreas PLA(2) (non-toxic) demonstrated that, in both cases, enzymatic hydrolysis of serum phospholipids present in the culture medium was responsible for parasite growth arrest. However, bee PLA(2)-lipolyzed serum induced stage-specific inhibition of P. falciparum development, whereas hog PLA(2)-lipolyzed serum killed parasites at either stage. Sensitivity to bee PLA(2)-treated serum appeared restricted to the 19-26-h period of the 48 h parasite cycle. Analysis of the respective role of the different lipoprotein classes as substrates of bee PLA(2) showed that enzyme treatment of high density lipoproteins, low density lipoproteins, and very low density lipoproteins/chylomicrons fractions induces cytotoxicity of either fraction. In conclusion, our results demonstrate that toxic and non-toxic PLA(2)s 1) are cytotoxic to P. falciparum via hydrolysis of lipoprotein phospholipids and 2) display different killing processes presumably involving lipoprotein by-products recognizing different targets on the infected red blood cell. more...
- Published
- 2000
- Full Text
- View/download PDF
50. Cloning of Plasmodium falciparum protein disulfide isomerase homologue by affinity purification using the antiplasmodial inhibitor 1,4-bis[3-[N-(cyclohexyl methyl)amino]propyl]piperazine..
- Author
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Florent I, Mouray E, Dali Ali F, Drobecq H, Girault S, Schrével J, Sergheraert C, and Grellier P
- Subjects
- Amino Acid Sequence, Animals, Base Sequence, Chromatography, Affinity, Chromatography, Gel, Cloning, Molecular, Colombia, Humans, Molecular Sequence Data, Molecular Weight, Plasmodium falciparum genetics, Plasmodium falciparum isolation & purification, Protein Disulfide-Isomerases isolation & purification, Protein Disulfide-Isomerases metabolism, Recombinant Proteins biosynthesis, Recombinant Proteins isolation & purification, Recombinant Proteins metabolism, Sequence Alignment, Sequence Homology, Amino Acid, Tanzania, Thailand, Antiprotozoal Agents, Plasmodium falciparum enzymology, Protein Disulfide-Isomerases genetics
- Abstract
A series of 10 1,4-bis(3-aminopropyl)piperazine compounds was found to display antiplasmodial activity with 50% growth inhibition between 30 and 250 nM, on three Plasmodium falciparum strains differently sensitive to chloroquine. By affinity chromatography using one of these compounds, a 52-kDa protein was isolated from P. falciparum, microsequenced and cloned. It corresponded to a single copy gene encoding a 453 amino acid protein displaying the typical features of protein disulfide isomerases, a thiol metabolizing enzyme belonging to the thiol: disulfide oxidoreductase superfamily, which was not previously described in malarial species. more...
- Published
- 2000
- Full Text
- View/download PDF
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