Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.53 (sialidase)
 2,694 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A genomic clone, pTt21, containing DNA apparently transcribed specifically in Trypanosoma cruzi trypomastigotes, was obtained by differentially screening a genomic library with trypomastigote and epimastigote cDNA. This 3444-bp clone contained open reading frames at each end, separated by a 1.8-kb non-coding region. The translated polypeptide from the 3' open reading frame (ORF2) of 1037 bp had 25-30% identity with 5 recently published T. cruzi gp85/sialidase sequences, and 20-25% identity with bacterial sialidases. Rabbit antiserum raised against an Escherichia coli fusion protein derived from the 5' open reading frame (ORF1) identified a surface antigen of 160 kDa, specifically expressed in trypomastigotes. A probe containing the first 211 bp from ORF1 was used to obtain a complete copy (c1821) of a gene that was closely related to ORF1, and encoded another member of the gp85/sialidase family. c1821 encodes a protein of 897 amino acids, but assignment of the N-terminus of the polypeptide was not possible. The 5'-most start codon is an unfavourable context to act as a translation initiator, it does not align with the initiator methionines of other gp85/sialidase sequences, nor is it followed by a signal peptide sequence characteristically found in other gp85/sialidase sequences. Although homology with the 5' ends of other gp85/sialidase sequences decays towards the 5' end of c1821, alignment of c1821 with 4 other gp85/sialidases indicated that the coding sequence should extend upstream at least 160 amino acids. In this region of c1821 there are multiple stop codons in each frame. The presence of the stop codons, the alignment data and our inability to amplify reverse transcribed mRNA using four internal primers, suggest that c1821 may not be present as a mature mRNA and is a pseudogene. Comparison of the apparently non-repetitive 3' coding domain of c1821 with the corresponding repetitive domains of two other members of the gp85/sialidase family revealed a high degree of similarity in nucleotide but not in amino acid sequence, and c1821 may thus represent an evolutionary intermediate between sub-families of the gp85/sialidase superfamily.
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PMID:Sequence homology and absence of mRNA defines a possible pseudogene member of the Trypanosoma cruzi gp85/sialidase multigene family. 147 90

We tested the immunogenicity of two Trypanosoma cruzi antigens injected into mice in the form of DNA vaccine. Immunization with DNA encoding dihydroorotate dehydrogenase did not confer protective immunity in all mouse strains tested. Immunization with DNA encoding trans-sialidase surface antigen (TSSA) protected C57BL/6 (H-2(b)) mice but not BALB/c (H-2(d)) or C3H/Hej (H-2(k)) mice against lethal T. cruzi infection. In vivo depletion of CD4(+) or CD8(+) T cells abolished the protective immunity elicited by TSSA gene in C57BL/6 mice. Enzyme-linked immunospot assay with splenocytes from T. cruzi-infected mice or TSSA gene-vaccinated mice identified an H-2K(b)-restricted antigenic peptide, ANYNFTLV. The CD8(+)-T-cell line specific for this peptide could recognize T. cruzi-infected cells in vitro and could protect naive mice from lethal infection when adoptively transferred. Coadministration of the interleukin-12 (IL-12) gene with the TSSA gene facilitated the induction of ANYNFTLV-specific CD8(+) T cells and improved the vaccine efficacy against lethal T. cruzi infection. These results reinforced the utility of immunomodulatory adjuvants such as IL-12 gene for eliciting protective immunity against intracellular parasites by DNA vaccination.
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PMID:Coadministration of an interleukin-12 gene and a Trypanosoma cruzi gene improves vaccine efficacy. 1218 27

Chronic infection with Trypanosoma cruzi causes significant morbidity and mortality. The parasite expresses on its surface and sheds into the extracellular milieu a large superfamily of trans-sialidase proteins. Previous studies have demonstrated that during T. cruzi infection, the trans-sialidase superfamily stimulates an antibody response, but how individuals respond to different proteins of the trans-sialidase superfamily remain poorly defined. In this report, we present an analysis of the antibody response of chronically infected individuals and inbred strains of mice to a panel of 11 different trans-sialidase proteins encoded by surface antigen 85 kD (SA85-1) genes. These data indicate that: (1) 90% of the individuals tested generated antibodies to one or more trans-sialidase proteins; (2) the individuals develop different patterns of antibody responsiveness to the panel of trans-sialidase proteins; (3) three inbred strains of mice develop trans-sialidase antibody responses, but each strain develops a different pattern of antibody response to the panel of trans-sialidase proteins; (4) the differences in the pattern of antibody response by the mouse strains are independent of MHC differences; and (5) trans-sialidase proteins that do not stimulate an antibody response during T. cruzi infection can stimulate a response following immunization. Together these data indicate that during T. cruzi infection individuals develop a diverse trans-sialidase antibody response that appears to be affected by genetic and environmental factors.
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PMID:Trypanosoma cruzi-infected individuals demonstrate varied antibody responses to a panel of trans-sialidase proteins encoded by SA85-1 genes. 1572 81

The membrane type sialidase (Neu3) has been suggested to participate in cell growth, migration and differentiation. To determine whether a Neu3 is able to modulate megakaryocytic differentiation of K562 cells, we studied the functional significance of human Neu3 induced by phorbol 12-myristate 13-acetate (PMA). Northern blot and reverse transcription-polymerase chain reaction (RT-PCR) indicated that the induction of hST3Gal V, which synthesizes ganglioside GM3 and reduction of Neu3 by PMA, are linked for the expression of differentiation marker protein, CD41b surface antigen. To elucidate the mechanism underlying the down-regulation of the CD41b surface antigen expression when Neu3 gene is expressed in PMA-treated cells, we characterized the Neu3-mediated signaling pathway. Neu3 overexpression inhibited the PMA-induced ERK1/2 and p38 MAPK phosphorylation in the K562 cells. Down-regulation of expression of CD41b surface antigen was dependent on expression of Neu3 gene. However, a Neu3 inhibitor Neu5Ac2en induced morphological changes, showing megakaryocytic differentiation of K562 cells, with expression of CD41b surface antigen, while a specific glucosylceramide synthase inhibitor PDMP inhibited megakaryocytic differentiation of K562 cells. The molecular mechanisms involved in Neu3-involved inhibition of CD41b surface antigen expression in K562 cells have been suggested: the Neu3 degrades membrane sialic acids and the resulting signaling pathway of the PKC/ERKs/p38 MAPK is down-regulated, causing a decrease in CD41b surface antigen expression and inhibition of megakaryocytic differentiation of K562 cells.
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PMID:Membrane type sialidase inhibits the megakaryocytic differentiation of human leukemia K562 cells. 1833 27

Trypanosoma cruzi is the etiologic agent of Chagas disease. Although this is not a free-living organism it has conserved a contractile vacuole complex (CVC) to regulate its osmolarity. This obligate intracellular pathogen is, in addition, dependent on surface proteins to invade its hosts. Here we used a combination of genetic and biochemical approaches to delineate the contribution of the CVC to the traffic of glycosylphosphatidylinositol (GPI)-anchored proteins to the plasma membrane of the parasite and promote host invasion. While T. cruzi Rab11 (GFP-TcRab11) localized to the CVC, a dominant negative (DN) mutant tagged with GFP (GFP-TcRab11DN) localized to the cytosol, and epimastigotes expressing this mutant were less responsive to hyposmotic and hyperosmotic stress. Mutant parasites were still able to differentiate into metacyclic forms and infect host cells. GPI-anchored trans-sialidase (TcTS), mucins of the 60-200 KDa family, and trypomastigote small surface antigen (TcTSSA II) co-localized with GFP-TcRab11 to the CVC during transformation of intracellular amastigotes into trypomastigotes. Mucins of the gp35/50 family also co-localized with the CVC during metacyclogenesis. Parasites expressing GFP-TcRab11DN prevented TcTS, but not other membrane proteins, from reaching the plasma membrane, and were less infective as compared to wild type cells. Incubation of these mutants in the presence of exogenous recombinant active, but not inactive, TcTS, and a sialic acid donor, before infecting host cells, partially rescued infectivity of trypomastigotes. Taking together these results reveal roles of TcRab11 in osmoregulation and trafficking of trans-sialidase to the plasma membrane, the role of trans-sialidase in promoting infection, and a novel unconventional mechanism of GPI-anchored protein secretion.
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PMID:Rab11 regulates trafficking of trans-sialidase to the plasma membrane through the contractile vacuole complex of Trypanosoma cruzi. 2496 13