Nucleotidase Cascades Are Catalyzed by Secreted Proteins of the Parasitic Nematode<i>Trichinella spiralis</i>

Gounaris, Kleoniki

doi:10.1128/iai.70.9.4917-4924.2002

Cited by 57 publications

(44 citation statements)

References 62 publications

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“…Exoenzymes: apyrase, 5'-nucleotidase, and adenosine deaminase are secreted by T. spiralis (Gounaris 2002). These proteins constitute an enzymatic cascade which catalyzes the degradation of extracellular nucleotides, with a potential physiological role in the regulation of purinergic signaling.…”

Section: Nucleotide-metabolizing Enzymesmentioning

confidence: 99%

Functional genes and proteins of Trichinella spp.

Nagano

Takahashi

2008

Parasitol Res

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Research of Trichinella proteins has been conducted with emphasis on excretory-secretory (E-S) products of muscle larvae because of two reasons. The first is that it has prominent and narrow specific antigenicity, and the second is that it may play some role in nurse cell formation after being secreted into host muscle cells. Proteomic analysis of E-S proteins was further advanced by the aid of new analytical methods such as gene cloning, matrix-assisted laser desorption-ionization time-of-flight mass spectrometry, and expressed sequence tags database analysis. As the research progressed, the interest of researchers moved to identification of function of E-S products, which has shed further light on the intriguing relationships between parasites and hosts. Major constituents of the E-S products include 43-, 53-, and 45-kDa glycoprotein derived from the stichosome. Many proteins were discovered in E-S products after the 43-, 53-, and 45-kDa proteins although the relationships among them remain unclear. Some of the new proteins were partially defined in terms of their function including nuclear antigens, MyoD-like protein, TsJ5 protein, etc. There are better-characterized proteins based on the gene molecular method, which allow easier identification of the function of proteins of interest. Such examples were demonstrated by proteinases, proteinase inhibitors, heat shock proteins, glycosidases, etc.

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Section: Nucleotide-metabolizing Enzymesmentioning

confidence: 99%

Functional genes and proteins of Trichinella spp.

Nagano

Takahashi

2008

Parasitol Res

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“…The ATP-utilizing enzymes are active mostly in the presence of ATP, operating through activation of the P2Z purinergic receptors (58). Indeed, similar modulation of purinergic receptor activation by secreted ATP-utilizing enzymes of the parasitic nematode Trichinella spiralis has recently been reported (9,10). In contrast, the azurin homologue triggers the release of mitochondrial cytochrome c to the cytosol (Fig.…”

Section: Discussionmentioning

confidence: 99%

Energy-Generating Enzymes ofBurkholderia cepaciaand Their Interactions with Macrophages

et al. 2003

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We previously demonstrated that several clinical and environmental isolates of Burkholderia cepacia secreted ATP-utilizing enzymes to the medium; the secretion of these enzymes by cystic fibrosis lung isolate strain 38 was shown to be greatly enhanced in the presence of ␣ 2 -macroglobulin. Fractionation of the growth medium of cystic fibrosis isolate strain 71 belonging to genomovar I demonstrated the presence of two additional proteins, homologues of Pseudomonas aeruginosa azurin and cytochrome c 551 , which are normally involved in electron transfer during denitrification. A Q-Sepharose column flowthrough fraction of the growth medium of B. cepacia strain 71 enriched with the azurin and cytochrome c 551 homologues triggered apoptosis in macrophages and mast cells, leading to their death. Incubation of the Q-Sepharose column flowthrough fraction with antiazurin and anti-cytochrome c 551 antibodies greatly reduced cell death. We cloned and hyperexpressed a gene from B. cepacia strain 71 that encodes the homologue of P. aeruginosa azurin. Such azurin homologues were detected in the growth medium of several strains belonging to genomovars I, III, and VI but not in the growth medium of strains belonging to other genomovars. The growth medium of the strains that elaborated the azurin homologue had high cytotoxicity towards macrophages. Purified azurin homologue was shown to induce apoptosis in macrophages in a caspase-dependent manner and was localized in both the cytosol and nucleus when incubated with or microinjected into macrophages. This is an interesting example of the interaction of a bacterial protein normally involved in cellular energetics with macrophages to effect their cell death.

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“…spiralis SP inhibited activation of mast cells by adenosine at concentrations of 10 M or less. This can most likely be attributed to an adenosine deaminase which we have shown to be secreted by the parasite (15). Increasing the concentration of adenosine to 100 M overcame the inhibition (data not shown), which would be limited by the concentration and specific activity of the enzyme in SP.…”

Section: Discussionmentioning

confidence: 99%

“…Infective larvae of Trichinella spiralis were recovered from Sprague-Dawley rats 2 months after oral infection and maintained in vitro, and secreted proteins (SP) were collected as previously described (15). The secreted 5=-NT was expressed in Pichia pastoris and purified from culture medium, again as previously described (17).…”

Section: Methodsmentioning

confidence: 99%

“…This process causes severe damage to mucosal tissue, which must result in the release of high concentrations of nucleotides into the extracellular environment. Interestingly, T. spiralis secretes a range of nucleotide-metabolizing enzymes, specifically a nucleoside diphosphate kinase (NDPK), a 5=-nucleotidase (5=-NT), and an adenosine deaminase (15,18). Secretion of these enzymes is anticipated to alter the amount and type of extracellular nucleotides available to bind host cell purinergic receptors, and we have postulated that these enzymes act to promote an anti-inflammatory environment that is more favorable for parasite survival (16).…”

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Trichinella spiralis Secreted Enzymes Regulate Nucleotide-Induced Mast Cell Activation and Release of Mouse Mast Cell Protease 1

et al. 2012

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Extracellular nucleotides are important triggers of innate immunity, acting on a wide variety of cells via signaling through purinergic receptors. Mucosal mast cells contribute to expulsion of a number of gastrointestinal nematode parasites, and mouse mast cell protease 1 has been shown to have a critical role in clearance of Trichinella spiralis from the intestinal tract. We show here that adenosine, ADP, ATP, UDP, and UTP all stimulate calcium mobilization in bone marrow-derived mast cells with a mucosal phenotype. Secreted proteins from T. spiralis infective larvae inhibit nucleotide-induced mast cell activation, and that induced by ADP and UDP is specifically blocked by parasite secretory 5=-nucleotidase. Release of mouse mast cell protease 1 is stimulated by ADP and ATP. Both parasite secreted products and the 5=-nucleotidase inhibit ADP-induced release of mast cell protease, whereas that stimulated by ATP is partially inhibited by secreted products alone. This indicates that the 5=-nucleotidase contributes to but is not solely responsible for inhibition of nucleotide-mediated effects on mast cell function. Secretion of nucleotide-metabolizing enzymes by parasitic nematodes most likely evolved as a strategy for suppression of innate immune responses and is discussed in this context.

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Nucleotidase Cascades Are Catalyzed by Secreted Proteins of the Parasitic NematodeTrichinella spiralis

Cited by 57 publications

References 62 publications

Functional genes and proteins of Trichinella spp.

Functional genes and proteins of Trichinella spp.

Energy-Generating Enzymes ofBurkholderia cepaciaand Their Interactions with Macrophages

Trichinella spiralis Secreted Enzymes Regulate Nucleotide-Induced Mast Cell Activation and Release of Mouse Mast Cell Protease 1

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