Abstract：
:The major proteolytic activity of Trypanosoma cruzi is a cathepsin L-like cysteine protease expressed in all stages of the parasite. As an initial step in identifying possible functions of this enzyme in the life cycle of T. cruzi, and examining its potential as a target for rational drug design, two fluoromethyl ketone-derivatized cysteine protease inhibitors were studied for their effects on T. cruzi infection of mammalian cells. Both inhibitors are irreversible substrate analogues with high specificity for cysteine proteases and minimal toxicity to mammalian cells. While micromolar concentrations of inhibitors had some effect on replication of all parasite stages, the most dramatic arrest of parasite replication occurred at the transformation of trypomastigote to amastigote, and also from amastigote to trypomastigote. It is therefore proposed that the enzyme functions in intracellular protein degradation in some stages of T. cruzi, but also in remodeling of the parasite during transformation between stages. Concentrations of inhibitors necessary to interrupt the parasite life cycle had no observable toxicity to macrophages, fibroblasts or epithelial cells in culture. Differential susceptibility of T. cruzi versus host cysteine proteases to fluoromethyl ketone protease inhibitors suggests that inhibition of the T. cruzi cysteine protease is a potential lead for new chemotherapy of Chagas' disease.
journal_name
Mol Biochem Parasitoljournal_title
Molecular and biochemical parasitologyauthors
Harth G,Andrews N,Mills AA,Engel JC,Smith R,McKerrow JHdoi
10.1016/0166-6851(93)90086-dsubject
Has Abstractpub_date
1993-03-01 00:00:00pages
17-24issue
1eissn
0166-6851issn
1872-9428pii
0166-6851(93)90086-Djournal_volume
58pub_type
杂志文章abstract：:Surface proteins of male and female gametes of Plasmodium gallinaceum were radioiodinated by the lactoperoxidase method, immunoprecipitated with stage specific antisera and separated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Stage specificity of the surface antigens was further studied by competiti...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/0166-6851(84)90061-6
更新日期：1984-04-01 00:00:00
abstract：:Given the growing appreciation of serious health sequelae from widespread Trichomonas vaginalis infection, new tools are needed to study the parasite's genetic diversity. To this end we have identified and characterized a panel of 21 microsatellites and six single-copy genes from the T. vaginalis genome, using seven l...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/j.molbiopara.2010.08.006
更新日期：2011-01-01 00:00:00
abstract：:The glycosylphosphatidylinositol (GPI)-anchored variant surface glycoprotein (VSG) of Trypanosoma brucei is the most abundant GPI-anchored protein expressed on any cell, and is an essential virulence factor. To determine what structural features affect efficient expression of VSG, we made a series of mutations in two ...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/s0166-6851(03)00055-0
更新日期：2003-05-01 00:00:00
abstract：:Giardia lamblia is an early diverging eukaryote which causes gastrointestinal disease throughout the world. Different subgroups of Giardia have been defined based on several biochemical and genetic criteria. We have developed a method for stably introducing DNA into the nuclei of the parasite using puromycin acetyltra...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/s0166-6851(97)00225-9
更新日期：1998-04-01 00:00:00
abstract：:The separation by chromatofocusing of two distinct purine nucleoside cleaving activities from crude extracts of Trypanosoma brucei brucei is described. One catalyzes the reversible phosphorolysis of 5'-deoxy-5'-methylthioadenosine (MeSAdo) and adenosine (Ado) and was designated an MeSAdo/Ado phosphorylase, while the o...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/0166-6851(88)90030-8
更新日期：1988-01-15 00:00:00
abstract：:Leishmania major promastigotes grown in late log phase were incubated with glucose as sole exogenous carbon source in the presence of 5% CO2 and the amounts of glucose consumed and of the major products formed--succinate, pyruvate, alanine, acetate, glycerol, and D-lactate--were measured as a function of pO2. Glucose ...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/0166-6851(90)90062-q
更新日期：1990-03-01 00:00:00
abstract：:We have cloned and sequenced a homologue of the ring-infected erythrocyte surface antigen (RESA) gene from Plasmodium falciparum designated RESA-2. Two reading frames with high homology to exon 1 and exon 2 of RESA at both the nucleotide and amino acid levels were identified in the RESA-2 sequence. However, RESA-2 doe...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/0166-6851(92)90113-x
更新日期：1992-09-01 00:00:00
abstract：:EP and GPEET procyclins are the major surface glycoproteins of Trypanosoma brucei in the midgut of tsetse flies (Glossina spp.). The procyclin genes are located at the beginning of polycistronic transcription units and are followed by at least one procyclin-associated gene (PAG). The EP/PAG1 locus on one copy of chrom...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/j.molbiopara.2006.07.005
更新日期：2006-12-01 00:00:00
abstract：:Superposition of two unrelated processes, namely terminal reticulocyte differentiation and synchronous plasmodial development, takes place in experimental infections of Plasmodium berghei. The first process is shown to be responsible for the appearance of some discrete restriction bands of host origin when DNA is extr...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/0166-6851(89)90107-2
更新日期：1989-11-01 00:00:00
abstract：:We have characterised the organisation of genes encoding the glutamate and alanine rich protein (GARP) surface coat of the procyclic and epimastigote stages of Trypanosoma congolense in the tsetse fly. The GARP genes are arranged at two, possibly physically linked, loci, one of which exhibits allelic variation. One lo...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/s0166-6851(99)00190-5
更新日期：2000-02-05 00:00:00
abstract：:Plasmodium falciparum trophozoites were isolated by mechanical rupture of infected human erythrocytes followed by a series of differential centrifugation steps. After lysis with sonication, the 100 000 x g supernatant of parasites and uninfected host cells was used to determine the specific activities of a number of e...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/0166-6851(82)90035-4
更新日期：1982-05-01 00:00:00
abstract：:Phosphoserine phosphatase (PSP) catalyzes the third step of the phosphorylated serine biosynthetic pathway, and occurred multiple times in evolution, while enzymes catalyzing the first and second steps in the pathway have single respective origins. In the present study, we examined the existence of PSP among genus Ent...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/j.molbiopara.2016.06.002
更新日期：2016-06-01 00:00:00
abstract：:Acetylcholinesterase (AChE) plays a key role in postsynaptic transmission in most animals. Nematodes encode multiple AChEs, implying its functional diversity. To explore physiological functions of multiple AChEs, three distinct AChEs (BxACE-1, BxACE-2, and BxACE-3) were identified and characterized from the pinewood n...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/j.molbiopara.2010.11.005
更新日期：2011-02-01 00:00:00
abstract：:The use of transfection in the study of the biology of malaria parasites has been limited due to poor transfection efficiencies (frequency of 10(-6) to 10(-9)) and a paucity of selection markers. Here, a new method of transfection, using non-viral Nucleofector technology, is described for the rodent parasite Plasmodiu...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/j.molbiopara.2005.09.007
更新日期：2006-01-01 00:00:00
abstract：:In Ascaris muscle mitochondria the major respiratory chain-linked phosphorylation activity is accomplished by a NADH-linked reduction of fumarate to succinate. Oxygen can also be employed as a terminal electron acceptor via a cyanide- and salicyl-hydroxamate-resistant terminal oxidase. As in fumarate-dependent electro...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/0166-6851(80)90002-x
更新日期：1980-04-01 00:00:00
abstract：:The Leishmania GP63 major surface protein gene family encodes multiple isoforms which differ predominantly in the carboxyterminal region. We have isolated 4 full-length gp63 cDNA clones derived from stationary-phase promastigote RNA of a cloned isolate of Leishmania guyanensis, a member of the braziliensis complex. Th...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/0166-6851(93)90107-9
更新日期：1993-12-01 00:00:00
abstract：:Precipitin arcs formed after immunoelectrophoresis of Schistosoma mansoni egg, worm and cercarial antigens with polyspecific rabbit antisera have been 'stained' at neutral pH with chromogenic enzyme substrates specific for proteases and peptidases. A total of 7 antigenically distinct enzymes with peptidolytic properti...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/0166-6851(88)90153-3
更新日期：1988-12-01 00:00:00
abstract：:The degree of polymorphism and the allelic distribution of 2 major Plasmodium falciparum merozoite surface antigens (MSA1 and MSA2) have been analysed in clinical isolates from Colombia. DNA was prepared directly from patients' blood and used in PCR reactions to amplify block 2 of MSA1 and the central region from MSA2...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/0166-6851(91)90070-m
更新日期：1991-12-01 00:00:00
abstract：:Cathepsin L-like activity was demonstrated in the excretory/secretory (E/S) products of Fasciola hepatica newly excysted juveniles (NEJ), 3-week-old, 5-week-old and mature flukes using the fluorogenic substituted 7-amino-4-methylcoumarin substrates Z-phe-arg-AMC, Z-arg-arg-AMC and Z-arg-AMC. Gelatin-substrate polyacry...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/0166-6851(93)90172-t
更新日期：1993-11-01 00:00:00
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
更新日期：1986-01-01 00:00:00
abstract：:Glucose is a major source of energy and carbon in promastigotes of Leishmania mexicana, and its uptake is mediated by three glucose transporters whose genes are encoded within a single cluster. A null mutant in which the glucose transporter gene cluster was deleted by homologous gene replacement was generated previous...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/j.molbiopara.2007.01.010
更新日期：2007-05-01 00:00:00
abstract：:A total of 518 expressed sequence tags (ESTs) have been generated from clones randomly selected from a cDNA library and a spliced leader sub-library of a Trypanosoma brucei rhodesiense bloodstream clone. 205 (39%) of the clones were identified based on matches to 113 unique genes in the public databases. Of these, 71 ...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/0166-6851(95)00098-l
更新日期：1995-07-01 00:00:00
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
更新日期：2011-02-01 00:00:00
abstract：:Toxocariasis is a neglected disease, and its main etiological agent is the nematode Toxocara canis. Serological diagnosis is performed by an enzyme-linked immunosorbent assay using T. canis excretory and secretory (TES) antigens produced by in vitro cultivation of larvae. Identification of TES proteins can be useful f...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/j.molbiopara.2016.09.002
更新日期：2017-01-01 00:00:00
abstract：:The cyclophilins are a large family of proteins implicated in folding, transport and regulation of other proteins and are potential drug targets in cancer and in some viral and parasitic infections. The functionality of cyclophilins appears to depend on peptidyl-prolyl cis-trans isomerase (foldase) and/or molecular ch...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/j.molbiopara.2012.04.006
更新日期：2012-07-01 00:00:00
abstract：:The reduction in hemozoin content is a well known feature of chloroquine-resistant Plasmodium berghei. Using NK65-derived lines displaying increasing resistance levels, we observed an inverse relationship between the hemozoin content, and the glutathione (GSH) and glutathione S-transferase (GST) levels. Treatment of h...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/s0166-6851(98)00170-4
更新日期：1999-01-25 00:00:00
abstract：:The influence of growth in the presence of nifurtimox on total lipids of Trypanosoma cruzi epimastigotes was determined. Nifurtimox-treated organisms showed greater amounts of unsaturated fatty acids as compared with control cells. 18:2 was the major component in the total esterified lipid fraction. Similar results we...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/0166-6851(86)90127-1
更新日期：1986-12-01 00:00:00
abstract：:Root-knot nematodes (Meloidogyne spp.) are among the most important plant pathogens. In this study, the mitochondrial (mt) genomes of the root-knot nematodes, M. chitwoodi and M. incognita were sequenced. PCR analyses suggest that both mt genomes are circular, with an estimated size of 19.7 and 18.6-19.1kb, respective...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/j.molbiopara.2014.04.003
更新日期：2014-03-01 00:00:00
abstract：:As genomic sequencing of Leishmania nears completion, functional analyses that provide a global genetic perspective on biological processes are important. Despite polycistronic transcription, RNA transcript abundance can be measured using microarrays. To provide a resource to evaluate cDNA arrays, we undertook 5' expr...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/j.molbiopara.2004.03.004
更新日期：2004-07-01 00:00:00
abstract：:Schistosomes have a complex life cycle (vertebrate and molluscan hosts as well as larvae living freely in water) in which they are exposed to different environments and temperatures (20 degrees C - 37 degrees C). Since heat shock genes are activated in response to stress and during development [1], it is of interest t...
journal_title：Molecular and biochemical parasitology
pub_type： 杂志文章
doi：10.1016/0166-6851(92)90188-p
更新日期：1992-12-01 00:00:00
