Characterization and localization of an ATP-diphosphohydrolase on the external surface of the tegument of Schistosoma mansoni

Vasconcelos, Eveline Gomes; Nascimento, Paulo S.; Nazareth, Michael R.; Meirelles, Lúcia Collares; Verjovski-Almeida, Sérgio; Ferreira, Sérgio T.

doi:10.1016/0166-6851(93)90042-v

Cited by 84 publications

(81 citation statements)

References 28 publications

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“…It has long been known that schistosome tegumental extracts do possess ATP-and ADP-hydrolyzing capabilities and that living worms can deplete exogenous ATP and ADP [10], and we have confirmed that living parasites (both adults and schistosomula) can degrade exogenous ATP, ADP, and AMP [12].…”

Section: Discussionsupporting

confidence: 78%

“…In addition, protein sequence analysis reveals that, unlike SmATPDase1, SmATPDase2 is devoid of a predicted canonical signal peptide (and any transmembrane domain) [18]. Since both SmATPDase1 and SmATPDase2 possess conserved catalytic regions, characteristic of NTPDase family members [10,11], it seems likely that SmATPDase2 (and not just SmATPDase1) is capable of degrading nucleotide tri-and di-phosphates. Since, as shown here, SmATPDase2 has no demonstrable impact on ATP and ADP levels external to the worm, we presume that this enzyme functions in the internal tissues of the parasites, and especially in eggs (see below).…”

Section: Discussionmentioning

confidence: 99%

“…Extracellular ATP can act as a proinflammatory immunomediator by acting on multiple immunological effector cell types including neutrophils, macrophages, dendritic cells, and lymphocytes (reviewed in [5,7,8]). It has been hypothesized that schistosome ectoenzymes can degrade exogenous ATP so as to impede host immune cell activation in the vicinity of the worms [9], and it has long been known that schistosome tegumental extracts do possess ATP and ADP hydrolyzing activity [10,11]. In fact, the worms possess a panel of three ectoenzymes at the host/parasite interface that have been hypothesized to catabolize exogenous ATP.…”

Section: Introductionmentioning

confidence: 99%

“…In this work, we classify both SmATPDase1 and SmATPDase2 as apyrases since they exhibit homology to cation-activated enzymes that catalyze the hydrolysis of ATP and ADP to generate AMP and inorganic phosphate [11,10]. Sequence comparisons more formally position both proteins in the GDA1_CD39 superfamily (also known as the nucleotide triphosphate diphosphohydrolases, NTPDases).…”

Section: Introductionmentioning

confidence: 99%

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Schistosome apyrase SmATPDase1, but not SmATPDase2, hydrolyses exogenous ATP and ADP

Da’dara¹,

Bhardwaj²,

Skelly³

2014

Purinergic Signalling

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Schistosomes are parasitic worms that can live in the bloodstream of their vertebrate hosts for many years. It has been proposed that the worms impinge on host purinergic signalling by degrading proinflammatory molecules like ATP as well as prothrombotic mediators like ADP. This capability may help explain the apparent refractoriness of the worms to both immune elimination and thrombus formation. Three distinct ectoenzymes, expressed at the host-exposed surface of the worm's tegument, are proposed to be involved in the catabolism of ATP and ADP. These are alkaline phosphatase (SmAP), phosphodiesterase (SmNPP-5), and ATP diphosphohydrolase (SmATPDase1). It has recently been shown that only one of these enzymes-SmATPDase1-actually degrades exogenous ATP and ADP. However, a second ATP diphosphohydrolase homolog (SmATPDase2) is located in the tegument and has been reported to be released by the worms. It is possible that this enzyme too participates in the cleavage of exogenous nucleotide tri-and di-phosphates. To test this hypothesis, we employed RNA interference (RNAi) to suppress the expression of the schistosome SmATPDase1 and SmATPDase2 genes. We find that only SmATPDase1-suppressed parasites are significantly impaired in their ability to degrade exogenously added ATP or ADP. Suppression of SmATPDase2 does not appreciably affect the worms' ability to catabolize ATP or ADP. Furthermore, we detect no evidence for the secretion or release of an ATP-hydrolyzing activity by cultured parasites. The results confirm the role of tegumental SmATPDase1, but not SmADTPDase2, in the degradation of the exogenous proinflammatory and prothrombotic nucleotides ATP and ADP by live intravascular stages of the parasite.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Schistosome apyrase SmATPDase1, but not SmATPDase2, hydrolyses exogenous ATP and ADP

Da’dara¹,

Bhardwaj²,

Skelly³

2014

Purinergic Signalling

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“…Two Schistosoma mansoni ATP diphosphohydrolase isoforms of approximately 63 kDa, which differ in their catalytic properties, solubilities and sensitivities to nonionic detergents, were partially purified from both adult worm tegument and homogenised egg preparations (Vasconcelos et al 1993, Faria-Pinto et al 2004). The cloning of two S. mansoni ATP diphosphohydrolase genes (SmATPDases 1 and 2) from the adult worm was reported and these genes were shown to encode proteins that belong to the ATP diphosphohydrolase family (DeMarco et al 2003, Levano-Garcia et al 2007.…”

mentioning

confidence: 99%

Immunostimulatory property of a synthetic peptide belonging to the soluble ATP diphosphohydro-lase isoform (SmATPDase 2) and immunolocalisation of this protein in the Schistosoma mansoni egg

Mendes

Gusmão

Maia

et al. 2011

Mem. Inst. Oswaldo Cruz

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A peptide (SmB2LJ; r175-194) that belongs to a conserved domain from Schistosoma mansoni SmATPDase 2 and is shared with potato apyrase, as predicted by in silico analysis as antigenic, was synthesised and its immunostimulatory property was analysed. When inoculated in BALB/c mice, this peptide induced high levels of SmB2LJ-specific IgG1 and IgG2a subtypes, as detected by enzyme linked immunosorbent assay. In addition, dot blots were found to be positive for immune sera against potato apyrase and SmB2LJ. These results suggest that the conserved domain r175-194 from the S. mansoni SmATPDase 2 is antigenic. Western blots were performed and the anti-SmB2LJ antibody recognised in adult worm (soluble worm antigen preparation) or soluble egg antigen antigenic preparations two bands of approximately 63 and 55 kDa, molecular masses similar to those predicted for adult worm SmATPDase 2. This finding strongly suggests the expression of this same isoform in S. mansoni eggs. To assess localisation of SmATPDase 2, confocal fluorescence microscopy was performed using cryostat sections of infected mouse liver and polyclonal antiserum against SmB2LJ. Positive reactions were identified on the external surface from the miracidium in von Lichtenberg's envelope and, in the outer side of the egg-shell, showing that this soluble isoform is secreted from the S. mansoni eggs

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Purinoceptors: Ontogeny and phylogeny

Burnstock

1996

Drug Dev. Res.

108

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Characterization and localization of an ATP-diphosphohydrolase on the external surface of the tegument of Schistosoma mansoni

Cited by 84 publications

References 28 publications

Schistosome apyrase SmATPDase1, but not SmATPDase2, hydrolyses exogenous ATP and ADP

Schistosome apyrase SmATPDase1, but not SmATPDase2, hydrolyses exogenous ATP and ADP

Immunostimulatory property of a synthetic peptide belonging to the soluble ATP diphosphohydro-lase isoform (SmATPDase 2) and immunolocalisation of this protein in the Schistosoma mansoni egg

Purinoceptors: Ontogeny and phylogeny

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