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

Abstract

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.

In Vitro and in Vivo Antischistosomal Activities of Chalcones

“…[12] However, considering that 1 and 3 could act notably on tegument, some important enzymes are expressed at the external surface of S. mansoni, such as the ATP diphosphohydrolases. [18,19] Then, we speculated if 1 and 3 could also act, like the chalcone cardamonin, [11] inhibiting S. mansoni ATP diphosphohydrolases. In this regard, the in vitro inhibitory activities of the S. mansoni ATP diphosphohydrolases were determined for 1 and 3.…”

Flavonoids and Sesquiterpene Lactones from Artemisia absinthium and Tanacetum parthenium against Schistosoma mansoni Worms

“…This structural group could react with nucleophiles, especially sulfhydryl groups of cysteine, by a Michael-type addition. Therefore, considering that in the tegument surface and tubercles of schistosomes there are several cysteine residues, parthenolide could react with those exposed sulfhydryl groups, causing morphological alterations and inhibiting a variety of enzymes in schistosomes tegument [28, 29]. Also, these chemical alkylating properties are not found in hydroxypelenolide (Figure 1), which could explain its inactivity in vitro against adult schistosomes.…”

<p>Basic Coagulation Profiles and Platelet Count Among <em>Schistosoma mansoni</em>-Infected Adults Attending Sanja Primary Hospital, Northwest Ethiopia</p>

“…This results in inhibition of ADP-mediated platelet activation and aggregation. [9][10][11] In this manner, the enzyme expressed at the tegumental surface helps to limit blood clot formation around the worms by acting as an anticoagulant and permit the parasites free movement within the vasculature. 11 Coagulation factors play a role in secondary hemostasis in conjugation with platelet and vascular endothelium.…”