In vitro cytocidal effects on Trypanosoma brucei and inhibition of Leishmania major GP63 by peptidomimetic metalloprotease inhibitors.

Abstract:

:Peptidomimetic inhibitors of mammalian zinc metalloproteases have been tested as potential agents for intervention in disease caused by kinetoplastid protozoa. Certain metalloprotease inhibitors were able to inhibit the release of variant surface glycoprotein from cultured transgenic procyclic Trypanosoma brucei, confirming our previous identification of a cell surface zinc metalloprotease activity in this stage of the trypanosome lifecycle [Bangs, JD et al. Expression of bloodstream variant surface glycoproteins in procyclic stage Trypanosoma brucei: role of GPI anchors in secretion, EMBO J. 1997;16:4285]. Selected peptidomimetics were also found to be toxic for cultured bloodstream trypanosomes with IC50 values in the low micromolar range. The paradigm for zinc metalloproteases in kinetoplastids are the GP63 surface enzymes of Leishmania. Peptidomimetics at low micromolar concentrations were able to inhibit in vitro cleavage of a synthetic peptide substrate by purified GP63 from L. major. Our results suggest that zinc metalloproteases perform essential functions in different stages of the trypanosome lifecycle and we hypothesize that these activities may be affected by the recently discovered trypanosomal homologues of GP63 [El-Sayed, NMA and Donelson, JE. African trypanosomes have differentially expressed genes encoding homologues of Leishmania GP63 surface protease, J. Biol. Chem. 1997;272:26742]. Development of higher affinity metalloprotease inhibitors may provide a novel avenue for treatment of parasitic diseases.

journal_name

Mol Biochem Parasitol

authors

Bangs JD,Ransom DA,Nimick M,Christie G,Hooper NM

doi

10.1016/s0166-6851(01)00244-4

subject

Has Abstract

pub_date

2001-04-25 00:00:00

pages

111-7

issue

1

eissn

0166-6851

issn

1872-9428

pii

S0166-6851(01)00244-4

journal_volume

114

pub_type

杂志文章
  • Purification and characterization of gamma-glutamylcysteine synthetase from Ascaris suum.

    abstract::We have purified and characterized the Ascaris suum gamma-glutamylcysteine synthetase, the rate-limiting step in the glutathione biosynthesis. The purified enzyme exhibited a specific activity of 18 U (mg protein)-1. Estimation of the molecular mass of the native enzyme by FPLC on Superdex S-200 revealed the presence ...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(94)00064-t

    authors: Hussein AS,Walter RD

    更新日期:1995-06-01 00:00:00

  • Regulation of hsp70 expression in Trypanosoma cruzi by temperature and growth phase.

    abstract::The steady-state level of the hsp70 mRNAs of Trypanosoma cruzi cultured at different temperatures and growth conditions has been analyzed by Northern blotting. We show that only one size class of hsp70 mRNA, of about 2.2 kb, is transcribed from the hsp70 cluster and that its transcription is constitutive at 28 degrees...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(92)90022-c

    authors: Requena JM,Jimenez-Ruiz A,Soto M,Assiego R,Santarén JF,Lopez MC,Patarroyo ME,Alonso C

    更新日期:1992-07-01 00:00:00

  • Cryptosporidium parvum cyclic GMP-dependent protein kinase (PKG): An essential mediator of merozoite egress.

    abstract::Cryptosporidiosis is an obligate intracellular pathogen causing diarrhea. Merozoite egress is essential for infection to spread between host cells. However, the mechanisms of egress have yet to be defined. We hypothesized that Cyclic GMP-Dependent Protein Kinase G (PKG) may be involved in Cryptosporidium egress. In th...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2020.111277

    authors: Nava S,Sadiqova A,Castellanos-Gonzalez A,White AC Jr

    更新日期:2020-05-01 00:00:00

  • Characterisation of the gene encoding a 104-kilodalton microneme-rhoptry protein of Theileria parva.

    abstract::A neutralizing antiserum, C16, raised against sporozoites of Theileria parva parva was used to screen a lambda gt11 expression library of T. parva parva (Muguga) genomic DNA fragments. Proteins encoded by one phage clone, lambda TpS-17, were reactive with the C16 antiserum. Detailed characterisation of the DNA insert ...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(90)90007-9

    authors: Iams KP,Young JR,Nene V,Desai J,Webster P,ole-MoiYoi OK,Musoke AJ

    更新日期:1990-02-01 00:00:00

  • The complexity of the secreted NPA and FAR lipid-binding protein families of Haemonchus contortus revealed by an iterative proteomics-bioinformatics approach.

    abstract::Two different classes of small nematode specific lipid-binding proteins, the nematode polyprotein allergens/antigens (NPAs) and the fatty acid- and retinol-binding (FAR) proteins, are secreted by helminth parasites. Until now, there was no evidence of the expression or secretion of these two families of proteins in Ha...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2009.07.001

    authors: Kuang L,Colgrave ML,Bagnall NH,Knox MR,Qian M,Wijffels G

    更新日期:2009-11-01 00:00:00

  • Cloning, heterologous expression in Escherichia coli and characterization of a protein disulfide isomerase from Fasciola hepatica.

    abstract::A Fasciola hepatica cDNA clone of 1752 bp was isolated from an adult worm cDNA expression library by immunological screening using a rabbit serum against the excretory-secretory antigens. The nucleotide sequence of the cDNA revealed the presence of an open reading frame of 489 codons which encoded a 55 kDa polypeptide...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/s0166-6851(02)00269-4

    authors: Salazar-Calderón M,Martín-Alonso JM,Castro AM,Parra F

    更新日期:2003-01-01 00:00:00

  • The cyst wall of Entamoeba invadens contains chitosan (deacetylated chitin).

    abstract::The cyst wall of Entamoeba invadens (Ei), a model for the human pathogen Entamoeba histolytica, contains chitin, which is a homopolymer of beta-1, 4-linked N-acetyl-glucosamine (GlcNAc). In fungi and in bacteria that make nodulation factors, chitin deacetylases make chitosan, which is a mixture of GlcNAc and glucosami...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2006.03.002

    authors: Das S,Van Dellen K,Bulik D,Magnelli P,Cui J,Head J,Robbins PW,Samuelson J

    更新日期:2006-07-01 00:00:00

  • Serological cross-reaction between high molecular weight proteins synthesized in blood schizonts of Plasmodium yoelii, Plasmodium chabaudi and Plasmodium falciparum.

    abstract::A 230 000 molecular weight (MW) Plasmodium yoelii protein, a 250 000 MW P. chabaudi protein and a 195 000 MW P. falciparum protein, identified using monoclonal antibodies, have similar characteristics, and have been implicated as protective antigens. In this study the serological relationship between these proteins wa...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(83)90096-8

    authors: Holder AA,Freeman RR,Newbold CI

    更新日期:1983-11-01 00:00:00

  • Characterization of trafficking pathways and membrane genesis in malaria-infected erythrocytes.

    abstract::The origin of membraneous structures in the cytoplasm of human erythrocytes infected with the malaria parasite, Plasmodium falciparum, was determined by confocal fluorescence imaging microscopy. When infectious merozoites invaded erythrocytes labeled with the fluorescent, lipophilic, non-exchangeable molecules DiIC16 ...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(94)90038-8

    authors: Pouvelle B,Gormley JA,Taraschi TF

    更新日期:1994-07-01 00:00:00

  • The 5' flanking sequence of a Trypanosoma brucei variable surface glycoprotein gene.

    abstract::The mechanism controlling transcription at several telomeric expression sites for variable surface glycoprotein (VSG) genes in Trypanosoma brucei is unknown. Most VSG genes in expression sites have a region 5' of the gene lacking restriction enzyme sites. This 'barren region' is involved in recombination events which ...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(87)90103-4

    authors: Shah JS,Young JR,Kimmel BE,Iams KP,Williams RO

    更新日期:1987-06-01 00:00:00

  • Yeast dihydroorotate dehydrogenase as a new selectable marker for Plasmodium falciparum transfection.

    abstract::Genetic manipulation of Plasmodium falciparum in culture through transfection has provided numerous insights into the molecular and cell biology of this parasite. The procedure is rather cumbersome, and is limited by the number of drug-resistant markers that can be used for selecting transfected parasites. Here we rep...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2011.01.004

    authors: Ganesan SM,Morrisey JM,Ke H,Painter HJ,Laroiya K,Phillips MA,Rathod PK,Mather MW,Vaidya AB

    更新日期:2011-05-01 00:00:00

  • Functional characterisation of a nematode secreted GM2-activator protein.

    abstract::We have identified a GM2-activator protein (GM2AP) with highly unusual properties secreted by the nematode parasite Trichinella spiralis. Expression in Pichia pastoris resulted in a hyperglycosylated protein of 28 kDa, but the 18 kDa native protein was not glycosylated. The parasite GM2AP does not facilitate degradati...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2006.02.014

    authors: Bruce AF,Gares MP,Selkirk ME,Gounaris K

    更新日期:2006-06-01 00:00:00

  • Cysteine proteinase of Entamoeba histolytica. I. Partial purification and action on different enzymes.

    abstract::A method for a 50-60-fold purification of a cysteine proteinase from trophozoites of Entamoeba histolytica using 35-80% ammonium sulphate fractionation, gel chromatography on Sephadex G-75, and preparative isoelectric focusing is described. The enzyme was examined for its proteolytic potencies towards native enzyme su...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(86)90054-x

    authors: Scholze H,Werries E

    更新日期:1986-01-01 00:00:00

  • Trypanosoma cruzi response to the oxidative stress generated by hydrogen peroxide.

    abstract::As an intracellular parasite, Trypanosoma cruzi is exposed to reactive oxygen species. The study of the proteins involved in the hydroperoxide detoxification cascade, tryparedoxin peroxidase included, may lead to the development of a more specific chemotherapy for Chagas'disease. In this work, the involvement of TcCPX...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2003.08.011

    authors: Finzi JK,Chiavegatto CW,Corat KF,Lopez JA,Cabrera OG,Mielniczki-Pereira AA,Colli W,Alves MJ,Gadelha FR

    更新日期:2004-01-01 00:00:00

  • A short interspersed repetitive element provides a new 3' acceptor site for trans-splicing in certain ribosomal P2 beta protein genes of Trypanosoma cruzi.

    abstract::Four Trypanosoma cruzi genomic DNA fragments carrying different TcP2 beta genes have been isolated and sequenced. Three of them had a single TcP2 beta gene, while the 3.8-kb-long DNA segment encoding the TcP2 beta-H1.8 locus showed two TcP2 beta genes arranged in tandem. These genes were physically connected by a 428-...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(94)00026-3

    authors: Vazquez MP,Schijman AG,Levin MJ

    更新日期:1994-04-01 00:00:00

  • Chemiluminescence enhancement by trypanocidal drugs and by inhibitors of antioxidant enzymes in Trypanosoma cruzi.

    abstract::The spontaneous emission of chemiluminescence by Trypanosoma cruzi epimastigotes was 133 +/- 5 counts s-1 (mg protein)-1. The measured intracellular steady state concentration of hydrogen peroxide in the same cells was 1.5 +/- 0.5 microM. These two values are about 12- and 15-times higher than the corresponding ones f...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(88)90093-x

    authors: Giulivi C,Turrens JF,Boveris A

    更新日期:1988-09-01 00:00:00

  • Peroxisomal targeting protein 14 (PEX14) from Leishmania donovani. Molecular, biochemical, and immunocytochemical characterization.

    abstract::Pathogens of the Leishmania and Trypanosoma genera compartmentalize glycolytic and other nutritional pathways in glycosomes, unique subcellular organelles related to the peroxisomes of mammals and yeasts. Most glycosomal proteins are targeted to the glycosomes by a COOH-terminal tripeptide signal similar to the peroxi...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/s0166-6851(02)00164-0

    authors: Jardim A,Rager N,Liu W,Ullman B

    更新日期:2002-09-01 00:00:00

  • The mitochondrial phosphate carrier TbMCP11 is essential for mitochondrial function in the procyclic form of Trypanosoma brucei.

    abstract::Conserved amongst all eukaryotes is a family of mitochondrial carrier proteins (SLC25A) responsible for the import of various solutes across the inner mitochondrial membrane. We previously reported that the human parasite Trypanosoma brucei possesses 26 SLC25A proteins (TbMCPs) amongst which two, TbMCP11 and TbMCP8, w...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2020.111275

    authors: Gao F,Voncken F,Colasante C

    更新日期:2020-05-01 00:00:00

  • Genetic and antigenic characterization of Babesia bovis merozoite spherical body protein Bb-1.

    abstract::A Babesia bovis merozoite protein, Bb-1, was localized by immunoelectron microscopy to an apical organelle known as the spherical body. This unique structure appears to be analogous to dense granules of other apicomplexan protozoa. Similar to previously described dense granule proteins of Plasmodium spp., Bb-1 is secr...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(94)00200-7

    authors: Hines SA,Palmer GH,Brown WC,McElwain TF,Suarez CE,Vidotto O,Rice-Ficht AC

    更新日期:1995-02-01 00:00:00

  • The proteasome-ubiquitin pathway in the Schistosoma mansoni egg has development- and morphology-specific characteristics.

    abstract::Schistosoma mansoni eggs, consisting of an ovum surrounded by nutritive vitelline cells packaged in a tanned protein shell, are produced by paired worms residing in the mesenteric veins of the human host. The vitelline cells are degraded as the larval miracidium matures, the fully developed egg either crossing the gut...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2010.10.005

    authors: Mathieson W,Castro-Borges W,Wilson RA

    更新日期:2011-02-01 00:00:00

  • Predicted structure of a major Schistosoma mansoni eggshell protein.

    abstract::The complete sequence for a major Schistosome mansoni eggshell protein gene has been determined from a genomic DNA fragment. The use of an open reading frame encoding a glycine-rich polypeptide was confirmed by in vitro translation of schistosome mRNA in the presence of [3H]glycine and comparison with the amino acid c...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(89)90124-2

    authors: Rodrigues V,Chaudhri M,Knight M,Meadows H,Chambers AE,Taylor WR,Kelly C,Simpson AJ

    更新日期:1989-01-01 00:00:00

  • Enhanced Ca2+ uptake by mouse erythrocytes in malarial (Plasmodium berghei) infection.

    abstract::Erythrocytes from Plasmodium berghei-infected mice on incubation either in plasma or artificial isotonic media showed an increase in uptake of 45Ca2+ compared with erythrocytes from uninfected mice. Infected cells (55% parasitaemia) incubated in plasma from normal or infected mice gave uptake rates of 9.8 and 8.1 nmol...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(83)90023-3

    authors: Krungkrai J,Yuthavong Y

    更新日期:1983-03-01 00:00:00

  • Anopheles gambiae laminin interacts with the P25 surface protein of Plasmodium berghei ookinetes.

    abstract::Laminin is a major constituent of the basal lamina surrounding the midgut of the malaria vectors that has been implicated in the development of the Plasmodium oocyst. In this report we describe the cloning of the Anopheles gambiae gene encoding the laminin gamma 1 polypeptide and follow its expression during mosquito ...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/s0166-6851(00)00371-6

    authors: Vlachou D,Lycett G,Sidén-Kiamos I,Blass C,Sinden RE,Louis C

    更新日期:2001-02-01 00:00:00

  • Microarray based analysis of temperature and oxidative stress induced messenger RNA in Schistosoma mansoni.

    abstract::The body's defense against schistosome infection can take many forms. For example, upon developing acute schistosomiasis, patients often have fever coinciding with larval maturation, migration and early oviposition. As the infection becomes established, the parasite comes under oxidative stress generated by the host i...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2008.08.004

    authors: Aragon AD,Imani RA,Blackburn VR,Cunningham C

    更新日期:2008-12-01 00:00:00

  • Some kinetic properties of pyruvate kinase from Trypanosoma brucei: influence of pH and fructose-1,6-diphosphate.

    abstract::The influence of pH on the activity of purified pyruvate kinase (ATP:pyruvate 2-O-phosphotransferase, EC 2.7.1.40) from Trypanosoma brucei has been studied. The Km for the coenzyme ADP is pH-dependent and shows the involvement of a dissociable group on the free enzyme with a pKa of 6.5-6.7. The cooperative interaction...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(81)90032-3

    authors: Flynn IW,Bowman IB

    更新日期:1981-11-01 00:00:00

  • SYBR, TaqMan, or both: highly sensitive, non-invasive detection of Cardicola blood fluke species in Southern Bluefin Tuna (Thunnus maccoyii).

    abstract::Three species of blood fluke from the genus Cardicola are known to parasitize and cause disease in Bluefin Tunas--C. forsteri, C. orientalis, and C. opisthorchis. Although initially believed to be separated by geography and host specificity, recent identification of at least two Cardicola spp. concurrently present wit...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2013.07.002

    authors: Polinski M,Hamilton DB,Nowak B,Bridle A

    更新日期:2013-09-01 00:00:00

  • The Haemonchus contortus UNC-49B subunit possesses the residues required for GABA sensitivity in homomeric and heteromeric channels.

    abstract::Hco-UNC-49 is a GABA receptor from the parasitic nematode Haemonchus contortus that has a relatively low overall sequence similarity to vertebrate GABA receptors but is very similar to the UNC-49 receptor found in the free living nematode Caenorhabditis elegans. While the nematode receptors do share >80% sequence simi...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2011.04.002

    authors: Accardi MV,Forrester SG

    更新日期:2011-07-01 00:00:00

  • Patterns of polymorphism in genomic regions flanking three highly polymorphic surface antigens in Plasmodium falciparum.

    abstract::Many surface antigens of the human malaria parasite Plasmodium falciparum show extraordinary diversity, with different alleles being so divergent as to be unalignable in some coding regions. To better understand the population history and modes of selection on such loci, we sequenced genomic regions flanking the highl...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2007.12.004

    authors: Amodu OK,Hartl DL,Roy SW

    更新日期:2008-05-01 00:00:00

  • The reversible effect of glucose on the energy metabolism of Schistosoma mansoni cercariae and schistosomula.

    abstract::This study on isolated cercarial bodies demonstrates that the biological transformation from cercaria to schistosomulum and the biochemical transition from an aerobic to an anaerobic energy metabolism are separate processes, which are not necessarily linked. The metabolic transition depends on the external glucose con...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(92)90202-u

    authors: Horemans AM,Tielens AG,van den Bergh SG

    更新日期:1992-03-01 00:00:00

  • Proteomic analysis of Schistosoma mansoni egg secretions.

    abstract::Schistosomiasis remains a largely neglected, global health problem. The morbid pathology of the disease stems from the host's inflammatory response to parasite eggs trapped in host tissues. Long term host/parasite survival is dependent upon the successful modulation of the acute pathological response, which is induced...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2007.06.002

    authors: Cass CL,Johnson JR,Califf LL,Xu T,Hernandez HJ,Stadecker MJ,Yates JR 3rd,Williams DL

    更新日期:2007-10-01 00:00:00