Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
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Schistosomula of Schistosoma mansoni which are mechanically transformed at 4 degrees C and are then incubated at 37 degrees C in defined medium spontaneously secrete two proteases, a major one of 28 kDa and a minor one of 60 kDa. These were purified by ion exchange chromatography on DEAE-cellulose and gel filtration on Ultrogel AcA 54 with yields of 33% and 29%, respectively. Both appeared as single bands by silver staining following sodium dodecyl sulphate-polyacrylamide gel electrophoresis analysis. The 28 kDa protease is a glycoprotein that has a pI of 11 or higher and an optimal activity around pH 9.0. It cleaves casein, gelatin and human C3 and C3b. It is metal-ion independent and is inhibited by diisopropyl fluorophosphate, phenylmethanesulfonyl fluoride, soy-bean trypsin inhibitor, alpha 1 antitrypsin, Zn2+ ions, sodium dodecyl sulphate and normal human serum. The 60 kDa protease is a glycoprotein with a pI of 9.2. It can also cleave casein and gelatin and its activity is inhibited by phenylmethanesulfonyl fluoride but not by diisopropyl fluorophosphate or sodium dodecyl sulphate. We suggest that these proteases may play a role during cercarial penetration of the skin and in shedding of the cercarial glycocalyx.
Mol Biochem Parasitol 1988 Jul
PMID:Purification and characterization of proteases secreted by transforming schistosomula of Schistosoma mansoni. 304 Dec 76

Two-dimensional gel electrophoresis of liver mRNA translation products and dot-blot hybridization revealed that the levels of mRNA encoding major urinary proteins were greatly reduced in mice infected with Schistosoma mansoni. Major urinary protein mRNA levels are known to be androgen regulated. Dot-blot hybridization analysis of RNAs from various mouse tissues with a variety of cDNA probes indicated that all androgen-regulated mRNAs tested were reduced in infected mice. Administration of testosterone to infected animals restored urinary major urinary protein levels. Direct measurement of serum testosterone levels and seminal vesicle weights confirmed that chronic schistosome infection reduces testosterone to castration levels in male mice.
Mol Biochem Parasitol 1986 Mar
PMID:Effects of Schistosoma mansoni on androgen regulated gene expression in the mouse. 308 57

One of the major proteins of eggs and miracidia (p40) of Schistosoma mansoni has an apparent molecular weight of 40,000 and elicits a strong immune response in over 90% of patients. The antigen consists of a family of at least four near identical proteins, probably encoded by a multi-gene family, and expression of the p40 polypeptides is differentially regulated around the parasite's life cycle. We have isolated and sequenced cDNA clones encoding two variants of the antigen and expressed one p40 clone in Escherichia coli. The fusion protein elicits antibodies which immunoprecipitate p40 and recognise antigens of identical sizes in S. haematobium and S. bovis. The open reading frame encoding this antigen specifies a protein which shares a block of sequence homology with alpha-crystallins and Drosophila small heat shock proteins.
Mol Biochem Parasitol 1986 Nov
PMID:Sequence and expression of a major egg antigen from Schistosoma mansoni. Homologies to heat shock proteins and alpha-crystallins. 309 39

We have identified and sequenced a cDNA clone of a mRNA found only in mature female schistosomes. This mRNA is not detectably synthesized by female worms from single sex infections (unisexual females), by males or by the developing miracidia in the eggs. The clone hybridises to a highly abundant polyadenylated mRNA of approximately 1500 nucleotides. The nucleotide sequence of the clone predicts a polypeptide comprising two repetitive regions. A pentapeptide repeat with the consensus sequence Gly-Tyr-Asp-Lys-Tyr, and a region rich in histidine residues. Hybrid selected mRNA translated in vitro with [3H]tyrosine as labelled amino acid yields a polypeptide of 48 kDa (p48) that corresponds to the major [3H]tyrosine labelled translation product of female worm total mRNA. p48 does not label with [35S]methionine and is absent from the translation products of male and unisexual female mRNAs. The amino acid sequence of p48 has significant homologies to silk moth chorion proteins and we suggest that it is one of the major components of the schistosome eggshell probably accounting for the high level of [3H]tyrosine incorporation into the vitellaria of Schistosoma mansoni. The tyrosine content of the polypeptide suggests that it may play a role in phenol oxidase mediated cross-linking of the schistosome eggshell and in support of this we find that mushroom phenol oxidase will cause the specific cross-linking of p48 in in vitro translation products.
Mol Biochem Parasitol 1987 Jan 02
PMID:Possible eggshell protein gene from Schistosoma mansoni. 310 Sep 49

The major cause of mortality in human schistosomiasis is the chronic granulomatous reaction of the liver tissue to Schistosoma mansoni eggs. Liver biopsy still provides the best evaluation of the degree of liver damage. However, liver biopsy does not provide an image of the dynamic process of fibrogenesis. Variations of concentrations of procollagen type III peptide in sera have been proposed to be significant markers of liver fibrosis. Thus, liver function tests in relation to histopathological diagnosis and procollagen type III peptide concentrations were studied in patients with schistosomiasis and revealed a high correlation between the serum procollagen type III peptide and the degree of fibrosis in liver tissue.
Exp Mol Pathol 1987 Jun
PMID:Serum concentration of N-terminal procollagen peptide of collagen type III in schistosomal liver fibrosis. 310 33

An expression plasmid pEx34b was used to synthesise parts of the 31/32 kDa Schistosoma mansoni antigens as fusions with the amino terminus of the phage MS2 polymerase. Purified MS2-schistosome fusion proteins reacted specifically in an enzyme-linked immunosorbent assay with sera from S. mansoni-infected patients. The observation that the majority of human sera tested recognised schistosome-specific epitopes, but not the MS2 polymerase fragment, suggests that the fusion proteins are useful for the immunodiagnosis of schistosomiasis and might be incorporated in a serological test system based on recombinant antigens.
Mol Biochem Parasitol 1988 Jan 15
PMID:Expression of diagnostic 31/32 kilodalton proteins of Schistosoma mansoni as fusions with bacteriophage MS2 polymerase. 312 31

Triton X-114 has been employed to isolate integral membrane proteins from Schistosoma japonicum and Schistosoma mansoni adult worms. Suitable marker molecules and antisera directed or raised against schistosome proteins partitioned by Triton X-114 extraction indicated that the phase separation and purification of integral membrane proteins had been successful and this fraction was free of contamination with aqueous (soluble) or secretory antigens. Two dimensional immunoblots further exemplified differences between antigens in the integral membrane protein extract and those of the aqueous fraction. Seven S. japonicum integral membrane proteins have been identified on immunoblots by serum from a hyperimmune and an infected rabbit and by sera from Philippine patients with a history of schistosomiasis japonica. Integral membrane proteins of S. mansoni and S. japonicum had surprisingly little conformity in the molecular weights and electrophoretic mobilities between the two species.
Mol Biochem Parasitol 1988 May
PMID:Immunoblotting analysis of the major integral membrane protein antigens of Schistosoma japonicum. 313 62

Serotonin-stimulated adenylate cyclase activity in the trematode parasite Schistosoma mansoni increases 40-50-fold during its development from newly transformed schistosomulum to adult. The role of GTP in activation of the enzyme at different stages of development was investigated. Adenylate cyclase can be activated by the non-hydrolyzable GTP analogs 5'-guanylylimidodiphosphate (GppNHp) and guanosine-5'-(3-O-thiotriphosphate) (GTP gamma S), as well as by sodium fluoride. Activation by GTP gamma S is competitively antagonized by GTP. Cholera toxin catalyzes the ADP-ribosylation of several proteins in both early schistosomula and adults. Proteins of 93 and 53 kDa are labeled in both stages, but the other proteins labeled appear to be different in the two stages. Adult schistosomes exhibit autoribosylation by cholera toxin in a broad band at 41 kDa, and this is not seen in schistosomula. The effect of cholera toxin on cyclase activity was to reduce activation by serotonin, GTP gamma S, and fluoride, all agents which act through the GTP binding protein. Cholera toxin treatment also inhibits activation by optimal levels of forskolin, a diterpene that acts at the catalytic subunit. Pertussis toxin had little effect on cyclase activity, although it catalyzed the ADP-ribosylation of a single protein band at 45 kDa in both stages. The results suggest that the GTP binding protein that mediates adenylate cyclase activation by serotonin is somewhat different from Gs in the adrenergic adenylate cyclase system. The pertussis toxin substrate in S. mansoni does not appear to function as Gi.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Biochem Parasitol 1988 Jul
PMID:GTP binding regulatory proteins of adenylate cyclase in Schistosoma mansoni at different stages of development. 313 95

Two enzymes, alkaline phosphatase and acetylcholinesterase (AChE), have been shown previously to be components of the surface of the trematode parasite Schistosoma mansoni. In this study we report that both these enzymes and other serine hydrolases are susceptible to release from the S. mansoni tegumental membrane by a phosphatidylinositol-specific phospholipase C (PIPLC) of bacterial origin. These data suggest that AChE and alkaline phosphatase of S. mansoni, as in higher organisms, are anchored to the membrane via covalently attached phosphatidylinositol. The release of AChE from the vesicular fraction of the parasite with PIPLC occurs in a concentration-dependent manner. Sucrose gradient centrifugation of the PIPLC-released AChE showed a single 8.3 S molecular form, similar to that observed for AChE solubilized by Triton X-100. PIPLC removed large amounts of AChE from the surface of intact schistosomula in culture, with no impairment of the viability of the parasite. In this case, an increase in the overall levels of AChE in the intact parasite was observed after addition of PIPLC.
Mol Biochem Parasitol 1988 Jun
PMID:Acetylcholinesterase in Schistosoma mansoni is anchored to the membrane via covalently attached phosphatidylinositol. 313 66

The effect of specific chemotherapy on hepatic fibrosis was studied in Swiss albino mice infected with Schistosoma mansoni. The effect of treatment with praziquantel at 8, 12, and 20 weeks postinfection on fibrosis was assessed by determination of total hepatic collagen content, ratio of type III/I + III collagen, granuloma volume, and histopathological examination of liver section. Total collagen content was reduced in mice treated at the 8th week of infection compared to respective infected controls. The ratio of type III/I collagen was within normal limits. The decrease in collagen deposition was not observed when treatment was given 12 or 20 weeks postinfection. Early specific treatment of schistosomiasis may be important in the therapeutic approach to the control of morbidity in schistosomiasis.
Exp Mol Pathol 1988 Oct
PMID:Effect of praziquantel on hepatic fibrosis in experimental Schistosomiasis mansoni. 313 42


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