Primary sequence heterogeneity and tissue expression of glutathione S-transferases of Fasciola hepatica

Wijffels, Gene; Sexton, Jennifer; Salvatore, Liliana; Pettitt, J. M.; Humphris, Danielle C.; Panaccio, Michael; Spithill, Terry W.

doi:10.1016/0014-4894(92)90142-w

Cited by 61 publications

(28 citation statements)

References 30 publications

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“…These reactions are mediated by glutathione S-transferase (GST) enzymes. In F. hepatica, as many as eight GST isoforms have been shown to be present (Wijffels et al 1992). Altered GST activity has been linked to salicylanilide resistance in F. hepatica (Miller et al 1994), as well as thiabendazole resistance (Kerboeuf and Aycardi 1999) and cambendazole resistance (Kawalek et al 1984) in H. contortus.…”

Section: Introductionmentioning

confidence: 99%

The comparative metabolism of triclabendazole sulphoxide by triclabendazole-susceptible and triclabendazole-resistant Fasciola hepatica

Robinson

Lawson

Trudgett

et al. 2004

Parasitology Research

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Benzimidazole anthelmintics are widely used against nematode, cestode and trematode parasites. The drugs undergo several enzyme-mediated reactions within the host animal that produce a number of metabolites. Although it has been shown that certain helminths, including Fasciola hepatica, can metabolise albendazole, nothing is known regarding the ability of the liver fluke to metabolise triclabendazole, which is the major flukicidal compound currently on the market. In the current study, adult triclabendazole-susceptible flukes were treated with triclabendazole sulphoxide in vitro, and the metabolism of the drug was monitored by high performance liquid chromatography. The data show that F. hepatica can metabolise triclabendazole sulphoxide into its relatively inert sulphone metabolite. Parallel experiments using triclabendazole-resistant flukes showed that the conversion of triclabendazole sulphoxide to triclabendazole sulphone was on average 20.29% greater in the resistant flukes compared with the susceptible flukes. The results are discussed with regard to the mechanism of triclabendazole resistance in F. hepatica.

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Section: Introductionmentioning

confidence: 99%

The comparative metabolism of triclabendazole sulphoxide by triclabendazole-susceptible and triclabendazole-resistant Fasciola hepatica

Robinson

Lawson

Trudgett

et al. 2004

Parasitology Research

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“…It is likely that this is contingent upon the dimeric nature of the GST-SH3 domain fusion proteins (61,62); as the tyrosine kinases Itk, Src, and Abl are not known to function as dimers, this raised the possibility that the binding of these SH3 domains to Sam 68 might represent artifacts of the fusion protein system. In order to address this issue, maltose-binding protein fusion proteins containing the Itk SH3 domain were generated.…”

Section: Sh3 Domains Bind Similar But Distinct Sets Of Cellularmentioning

confidence: 99%

Identification of Itk/Tsk Src Homology 3 Domain Ligands

Bunnell

Henry²,

Kolluri³

et al. 1996

Journal of Biological Chemistry

179

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The tyrosine kinase Itk/Tsk is a T cell specific analog of Btk, the tyrosine kinase defective in the human immunodeficiency X-linked agammaglobulinemia and in xid mice. T lymphocytes from Itk-deficient mice are refractory to mitogenic stimuli delivered through the T cell receptor (TCR). To gain insights into the biochemical role of Itk, the binding properties of the Itk SH3 domain were examined. An optimal Itk SH3 binding motif was derived by screening biased phage display libraries; peptides based on this motif bound with high affinity and selectivity to the Itk SH3 domain. The T cell specific tyrosine kinase Tsk/Itk/Emt (1-4) (hereafter referred to as Itk) is a member of the Tec family of nonreceptor tyrosine kinases. This family of kinases consists of Tec, Btk, 1 Itk, and Bmx (5-7), and is defined by the presence of SH3 and SH2 domains (8) adjacent to the catalytic domain and an amino-terminal region containing a pleckstrin homology (PH) domain (9), a Tec homology (TH) domain (10), and a proline-rich region (11). Btk, the best characterized member of this family, is an important component of antigen receptor signaling pathways in B cells and mast cells (12-15). The expression pattern of Itk complements that of Btk; Itk is expressed in T cells whereas Btk is expressed in most hematopoietic cells other than T cells (16). This reciprocal pattern of expression suggests that these two kinases play analogous roles in antigen receptor signaling pathways, as is the case with ZAP-70 and Syk, which are capable of functionally substituting for one another (17).Btk has been identified as the gene defective in murine X-linked immunodeficiency (xid) (18, 19) and human X-linked agammaglobulinemia (XLA) (20,21). In xid mice, B cell numbers are reduced to one-half of normal and the titers of specific immunoglobulin isotypes are significantly reduced; in addition, xid B cells are insensitive to a number of mitogenic stimuli (22, 23). For reasons which have yet to be elucidated, the human disorder is much more severe, resulting in nearly complete elimination of the B cell compartment and dramatically reduced immunoglobulin levels (24). Biochemical studies have supported multiple roles for Btk in B cell activation. Btk kinase activity and tyrosine phosphorylation are increased after crosslinking either the B cell receptor on B cells (13-15) or the high affinity IgE receptor, Fc⑀RI, on mast cells (12). Interleukin-5 (25) and interleukin-6 (26) treatment have also been shown to lead to the activation of Btk.Itk, like Btk, is tyrosine-phosphorylated upon antigen receptor cross-linking (27).2 In addition, peripheral T cells from mice lacking functional Itk are refractory to stimulation by antibodies to CD3 plus antigen presenting cells (28). These Itk-deficient T cells can be stimulated by phorbol ester and calcium ionophore, demonstrating that Itk acts in signaling pathways proximal to the TCR. However, the manner in which Itk activity is regulated by, and integrated with, other TCR-derived signals is not well understood. Unlike th...

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“…The identification of such molecules could represent specific markers for the detection of F. hepatica. In this context, several molecules present in ESP have been characterized, including the cathepsin family of cysteine proteases (11), CuZn superoxide dismutase (25,43), enolase (5,24), fatty acid binding proteins (21), glutathione S-transferases (9,64), leucine aminopeptidase (LAP) (1), saposin-like molecules (15,19,48), and thioredoxin-associated proteins (23,24,29,32,36,51,52,56,57).…”

mentioning

confidence: 99%

Leucine Aminopeptidase Is an Immunodominant Antigen of Fasciola hepatica Excretory and Secretory Products in Human Infections

Marcilla

Rubia

Sotillo

et al. 2008

Clin Vaccine Immunol

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The liver fluke Fasciola hepatica parasitizes humans and ruminant livestock worldwide, and it is now being considered a reemerging zoonotic disease, especially in areas in which it is endemic, such as South America. This study investigates the immune response to excretory and secretory products produced by F. hepatica in a group of patients from the Peruvian Altiplano, where the disease is highly endemic. Using a proteomic approach and immunoblotting techniques, we have identified the enzymes leucine aminopeptidase (LAP) and phosphoenolpyruvate carboxykinase as immunodominant antigens recognized by sera from fasciolosis patients. An indirect enzyme-linked immunosorbent assay using recombinant LAP as the antigen was developed to check sera from individuals of this region. Our results demonstrate that LAP produces a specific and strong reaction, suggesting its potential use in the serologic diagnosis of F. hepatica infections in humans.

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Primary sequence heterogeneity and tissue expression of glutathione S-transferases of Fasciola hepatica

Cited by 61 publications

References 30 publications

The comparative metabolism of triclabendazole sulphoxide by triclabendazole-susceptible and triclabendazole-resistant Fasciola hepatica

The comparative metabolism of triclabendazole sulphoxide by triclabendazole-susceptible and triclabendazole-resistant Fasciola hepatica

Identification of Itk/Tsk Src Homology 3 Domain Ligands

Leucine Aminopeptidase Is an Immunodominant Antigen of Fasciola hepatica Excretory and Secretory Products in Human Infections

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