Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Smalpha is a short interspersed element (SINE)-like retroposon that occurs in high copy number of the genome of the human blood fluke Schistosoma mansoni. The sequence of the consensus Smalpha element includes the hallmark features of SINE-like elements including a promoter region for RNA polymerase III, an AT-rich stretch at its 3'-terminus, a short length of 500 bp or less, and short direct repeat sequences flanking the insertion site. Interestingly, the sequence of Smalpha also encodes an active ribozyme bearing a hammerhead domain. Contrary to the recent findings of Ferbeyre et al. (Mol. Cell. Biol. 18 (1998) 3880-8) that indicated that Smalpha-like elements were absent from the genome of the Oriental blood fluke Schistosoma japonicum, we report here that the genome of S. japonicum does contain a family of Smalpha-like retroposons, elements that we have named the Sjalpha family. Like Smalpha, Sjalpha elements are SINE-like in structure and sequence, are present at high copy number interspersed throughout the S. japonicum genome, and contain an ostensibly functional, hammerhead ribozyme motif. The presence of these elements in all species of Schistosoma so far examined suggests that the hammerhead domain was acquired by vertical transmission from a common schistosome ancestor.
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PMID:Sjalpha elements, short interspersed element-like retroposons bearing a hammerhead ribozyme motif from the genome of the oriental blood fluke Schistosoma japonicum. 1100 17

Schistosomes feed on human blood. They employ proteases to degrade hemoglobin from ingested erythrocytes, using the residues released for amino acid metabolism. However, the identity and the role of the participating protease(s) are unclear and controversial. Confocal microscopy localized schistosomal cathepsin D to the parasite gastrodermis, and revealed elevated protease expression in females. At sub-cellular level, cathepsin D was localized to superficial digestive vacuoles of the gut and to cisternae of the gastrodermal rough endoplasmic reticulum. Schistosome cathepsin D, expressed in insect cells, autoactivated at pH 3.6 to a approximately 40 kDa form that cleaved the substrates o-aminobenzoyl-Ile-Glu-Phe-nitroPhe-Arg-leu-NH(2) and hemoglobin. The NH(2)-terminal residues of mature cathepsin D of Schistosoma japonicum and Schistosoma mansoni were Asn1 and Gly1, respectively, revealing that the proregion peptide was comprised of 35 residues. The proteases cleaved hemoglobin at pH 2.5--4.6, releasing numerous fragments. S. Japonicum cathepsin D cleaved at 13 sites, S. mansoni cathepsin D at 15 sites. Early cleavage sites were alpha Phe33-Leu34 and beta Phe41-Phe42, while others included alpha Leu109-Ala-110 and beta Leu14-Trp15, demonstrating a preference for bulky hydrophobic residues at P1 and P1'. Most of the schistosomal cathepsin D cleavage sites were discrete from those of human cathepsin D. The gastrodermal location, elevated expression in females, acidic pH optima, similar substrate preferences in two species, and the discrete substrate preferences compared with human cathepsin D together provide compelling support for the hypothesis that schistosomal cathepsin D plays an integral role in hemoglobin proteolysis, and might be selectively targeted by drugs based on protease inhibition.
Mol Biochem Parasitol 2001 Jan 15
PMID:Proteolysis of human hemoglobin by schistosome cathepsin D. 1116 91

In biliary passages, Clonorchis sinensis causes epithelial hyperplasia and is assumed to promote carcinogenesis. Glutathione S-transferase (GST) is an antioxidant enzyme involved in phase II defense in trematodes. A clone (pcsGSTM1) encoding a GST was identified by screening a C. sinensis cDNA library with a PCR-synthesized cDNA probe. The predicted amino acid sequence encoded by pcsGSTM1 cDNA had a high degree of sequence identity and folding topology similar to the mu-class GSTs. The estimated molecular mass of the protein, 26 kDa, was consistent with an expression by pcsGSTM1 cDNA. The bacterially expressed recombinant csGSTM1 protein possessed an enzymatic GST activity and conjugated GSH to reactive carbonyls of lipid peroxidation. The recombinant csGSTM1 protein did not share antigenic epitope(s) with GSTs of Fasciola hepatica, Paragonimus westermani and Schistosoma japonicum. The csGSTM1 was identified to a mu-class GST in C. sinensis.
Mol Biochem Parasitol 2001 Jun
PMID:Molecular cloning and characterization of a mu-class glutathione S-transferase from Clonorchis sinensis. 1137 41

Schistosomiasis is one of the most serious parasitic diseases. More than 250 million people are infected with schistosomes in the tropics or subtropics. The parasitic flukes have some unique biological features: dioecism, complex life cycles, mechanisms to avoid host immune responses, and an apparent reliance on host endocrine and immune signals to complete their development, maturation and egg production. Recently, a large dataset of expressed sequence tags (ESTs) were generated from Schistosoma japonicum and Schistosoma mansoni, from which numerous novel genes were identified. The transcriptome analyses provide the basis for a comprehensive understanding of the molecular mechanisms involved in schistosome nutrition and metabolism, host-dependent development and maturation, immune evasion and invertebrate evolution. In addition, new potential vaccine candidates and drug targets have been predicted.
Trends Mol Med 2004 May
PMID:Schistosome transcriptomes: new insights into the parasite and schistosomiasis. 1512 Oct 48

Host inflammatory responses directed against eggs laid by sexually-mature Schistosoma japonicum female worms instigate lesion formation and associated clinical pathologies during infection. To identify parasite gene transcripts that associate with egg production and to characterise sexually-mature adult gene expression profiles of two related Chinese strains, S. japonicum cDNA microarrays were fabricated using 457 ESTs originating from three parasite developmental stages. Twenty-two female-associated and 8 male-associated gene transcripts were identified in the adult Anhui strain whereas 21 female-associated and 7 male-associated gene transcripts were revealed in the adult Zhejiang strain. RT-PCR analysis, in situ enzyme localisation studies and enzymatic assays confirmed the cDNA microarray results, and importantly, provided information previously unappreciated in schistosome conjugal biology. Specifically, our novel findings include the female-specific expression of genes putatively involved in haemoglobin digestion and eggshell formation including extracellular superoxide dismutase, two histidine-rich proteins, a large blood-brain barrier amino acid transporter and two tyrosinase orthologues. In contrast, transcripts involved in mechanical support (actin), cytoskeletal infrastructure (e.g. dynein light chain 3 and myosin regulatory light chain) and tegumental biology (e.g. TM4SF and Sj25) were more highly represented in adult male schistosomes. Together these data establish a transcriptional basis for adult schistosome labour division and expands the list of novel S. japonicum gender-associated gene transcripts that may be considered targets for improved intervention strategies.
Mol Biochem Parasitol 2004 Aug
PMID:Gender-associated gene expression in two related strains of Schistosoma japonicum. 1547 98

This study presents the first microsatellite investigation into the level of genetic variation among Schistosoma japonicum from different geographical origins. S. japonicum isolates were obtained from seven endemic provinces across mainland China: Zhejiang (Jiashan County), Anhui (Guichi County), Jiangxi (Yongxiu County), Hubei (Wuhan County), Hunan (Yueyang area), Sichuan 1 (Maoshan County), Sichuan 2 (Tianquan County), Yunnan (Dali County), and also one province in the Philippines (Sorsogon). DNA from 20 individuals from each origin were screened against 11 recently isolated and characterized S. japonicum microsatellites, and a set of nine loci were selected based on their polymorphic information content. High levels of polymorphism were obtained between and within population samples, with Chinese and Philippine strains appearing to follow different lineages, and with distinct branching between provinces. Moreover, across mainland China, genotype clustering appeared to be related to habitat type and/or intermediate host morph. These results highlight the suitability of microsatellites for population genetic studies of S. japonicum and suggest that there may be different strains of S. japonicum circulating in mainland China.
Mol Ecol 2005 Mar
PMID:An insight into the genetic variation of Schistosoma japonicum in mainland China using DNA microsatellite markers. 1572 75

We report on a sensitive, specific and easy to interpret PCR based diagnostic tool for the detection of Schistosoma japonicum eggs in the faeces of infected mammalian hosts. Primer pairs were designed to amplify regions of the mitochondrial DNA of the parasite. The specificity of the PCR primers was tested using either faecal samples from non-infected hosts or hosts infected with the related schistosome species S. mansoni. Sensitivity was investigated in a study, which differentiated the presence or absence of eggs in faecal samples. PCR results were correlated with analysis of the samples by microscopy. PCR analysis provided a level of sensitivity of 87.7%, while specificity was 100%. The PCR-based assay could detect mitochondrial DNA from as little as 0.3 of a single egg. The overall detection threshold of the PCR test was >or=60 eggs per gram of faeces. Advantages of this technique include the ability to scale-up screening and the reproducibility and simplicity of interpretation of results compared with standard microscopic methods.
Mol Cell Probes 2005 Aug
PMID:Copro-PCR based detection of Schistosoma eggs using mitochondrial DNA markers. 1603 93

In an attempt to isolate and characterize peptides mimicking epitopes of metalloprotease and explore their immunological protection against Schistosoma japonicum (S. japonicum), polyclonal anti-metalloprotease sera was prepared to screen a 12-mer random peptide library to isolate phages binding specially to antisera IgG. Then, phage ELISA, animal immunization, DNA sequencing, Western blotting and enzymatic activity neutralizing analysis were used to characterize the selected phage clones. All of ten randomly picked clones were shown to be positive. Five peptides of different amino acid sequences deduced from DNA sequences were obtained and two of them (peptides 2 and 3) could induce significant reduction (31.0% and 31.8%, respectively) in worm burden and high reduction (52.6% and 54.9%, respectively) in liver eggs per gram (LEPG), while, unexpectedly, others (peptides 1, 4 and 5) could not elicit enough protection against infection of S. japonicum. Peptides 2 and 3 could be recognized by S. japonicum infected mouse sera (IMS) and could elicit neutralizing Abs. The results show that peptides 2 and 3 are antigenic and immunogenic. They are true mimics of epitopes of metalloprotease and useful as novel vaccine candidates against S. japonicum.
Cell Mol Immunol 2005 Jun
PMID:Identification and characterization of peptides mimicking the epitopes of metalloprotease of Schistosoma japonicum. 1621 90

A metabolic profiling strategy was used to investigate the metabolic responses of Syrian hamsters (SLAC) to a Schistosoma japonicum infection using high resolution 1H nuclear magnetic resonance (NMR) spectroscopy and pattern recognition. In two independent experiments, male hamsters were each infected with 100 S. japonicum cercariae. At days 34-36 post-infection, urine was obtained from hamsters housed individually in metabolism cages. At the same time, urine was collected from age- and sex-matched infection-free control hamsters. The main biochemical effects of a S. japonicum infection in the hamster consisted of reduced levels of urinary tricarboxylic acid cycle intermediates, including citrate and succinate and increased levels of pyruvate. In addition, a range of microbial-related metabolites, such as hippurate, p-cresol glucuronide, phenylacetylglycine and trimethylamine were also associated with a S. japonicum infection. Most of the observed biochemical effects were in common with those previously characterized for a S. mansoni infection in a mouse host. The major distinguishing consequence of a S. japonicum infection in the hamster was the inhibition of manufacture or utilization of short-chain fatty acids, when compared to a S. mansoni infection in the mouse.
Mol Biochem Parasitol 2006 Mar
PMID:System level metabolic effects of a Schistosoma japonicum infection in the Syrian hamster. 1633 85

Complete mitochondrial genome sequences for the schistosomes Schistosoma haematobium and Schistosoma. spindale have been characterized. S. haematobium is the causative agent of urinary schistosomiasis in humans and S. spindale uses ruminants as its definitive host; both are transmitted by freshwater snail intermediate hosts. Results confirm a major gene order rearrangement among schistosomes in all traditional Schistosoma species groups other than Schistosoma japonicum; i.e., species groups S. mansoni, S. haematobium, and S. indicum. These data lend support to the 'out of Asia' (East and Southeast Asia) hypothesis for Schistosoma. The gene order change involves translocation of atp6-nad2-trnA and a rearrangement of nad3-nad1 relative to other parasitic flatworm mt genomes so far sequenced. Gene order and tRNA secondary structure changes (loss and acquisition of the DHU and/or TPsiC arms of trnC, trnF, and trnR) between mitochondrial genomes of these and other (digenean and cestode) flatworms were inferred by character mapping onto a phylogeny estimated from nuclear small subunit rRNA gene sequences of these same species, in order to find additional rare genomic changes suitable as synapomorphies. Denser and wider taxon sampling of mt genomes across the Platyhelminthes will validate these putative characters.
Mol Phylogenet Evol 2006 May
PMID:The complete mitochondrial genomes of Schistosoma haematobium and Schistosoma spindale and the evolutionary history of mitochondrial genome changes among parasitic flatworms. 1646 18


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