Leishmania (Viannia) braziliensis nucleoside triphosphate diphosphohydrolase (NTPDase 1): Localization and in vitro inhibition of promastigotes growth by polyclonal antibodies

Porcino, Gabriane Nascimento; Carvalho-Campos, C.; Maia, Ana Carolina Ribeiro Gomes; Detoni, Michelle Lima; Pinto, Priscila de Faria; Coimbra, Elaine Soares; Marques, Marcos José; Juliano, María A.; Juliano, Luiz; Diniz, Vanessa Alvaro; Cortê-Real, Suzana; Vasconcelos, Eveline Gomes

doi:10.1016/j.exppara.2012.08.009

Cited by 16 publications

(13 citation statements)

References 38 publications

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“…To verify the subcellular localization of this enzyme, the authors performed immunofluorescence assays in nonpermeabilized cells using a purified antibody against the recombinant E-NTPDase. The proteins were observed on cell body surfaces, especially at the anterior end of the cell, and no fluorescence was observed in the flagella, similar to the distribution found in other trypanosomatids (Pinheiro et al, 2006;Porcino et al, 2012;Mariotini-Moura et al, 2013). In fact, a more detailed investigation using electron microscopy confirmed the presence of E-NTPDases on the cell surface, corroborating the ecto-nucleotidase activity and confocal microscopy data.…”

Section: Leishmania Infantum Ntpdasessupporting

confidence: 81%

“…In addition to its ability to hydrolyze adenine nucleotides (ATP and ADP), rLicNTPDase‐2 was also able to hydrolyze uridine nucleotides (UTP and UDP), which led the authors to suggest that LicNTPDase‐2 could be involved in modulating the host's immune system by decreasing the inflammatory response. In fact, NTPDases have been implicated in the virulence and replication of trypanosomatids (Meyer‐Fernandes et al, ; Sansom et al, ; Santos et al, ; Marques‐da‐Silva et al, ; Porcino et al, ). For this reason, studies of these enzymes, including the elucidation of the protein crystal structure, could contribute to a better understanding of their involvement on infectivity and virulence of L. infantum .…”

Section: Leishmania Infantum Ntpdasesmentioning

confidence: 99%

“…The high antibody reactivity with either r‐pot B domains or the synthetic peptides LbB1LJ and LbB2LJ that was observed in L. amazonensis ‐infected BALB/c mice indicates the antigenicity of the B domain from the NTPDase‐1 isoform. In addition, measurements carried out throughout the disease progression revealed that the conserved B domain and its derivative synthetic peptides are able to induce the production of IgG1 and IgG2a, which have been shown to be able to inhibit the parasite NTPDase activity in vitro and/or promastigote proliferation (Maia et al, , ; Porcino et al, ). These results confirm the hypothesis that the conserved B domain, not only from L. amazonensis NTPDase‐1 but also from other Leishmania spp NTPDase‐1 isoforms, is also a target for the host immune response and contributes to both disease immunomodulation and mechanisms that mediate susceptibility or resistance to infection.…”

Section: Leishmania Ntpdases Antigenicitymentioning

confidence: 99%

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NTPDase activities: possible roles on Leishmania spp infectivity and virulence

Paes-Vieira

Gomes-Vieira

Meyer‐Fernandes

2018

Cell Biology International

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Nucleoside triphosphate diphosphohydrolases (NTPDases) are enzymes that belong to the GDA1/CD39 protein superfamily. These enzymes catalyze the hydrolysis of ATP and ADP to the monophosphate form (AMP). Biochemical characterization of the nucleotidases/NTPDases from various types of cells, including those from plants, animals, and pathogenic organisms, has revealed the existence of several isoforms with different specificities with respect to divalent cations (magnesium, calcium, manganese, and zinc) and substrates. In mammals, the NTPDases play important roles in the regulation of thrombosis and inflammation. In parasites of the genus Leishmania, the causative agents of leishmaniasis, two NTPDase isoforms, termed NTPDase-1 and NTPDase-2 have been described. Independently of their cellular localization, whether cell-surface localized, secreted or targeted to other organelles, in some Leishmania species these NTPDases could be involved in parasite growth, infectivity, and virulence. Experimental evidence has suggested that the hydrolysis of ATP and ADP by parasite ecto-nucleotidases can down-modulate the host immune response. In this context, the present work provides an overview of recent works that show strong evidence not only of the involvement of the nucleotidases/NTPDases in Leishmania spp infectivity and virulence but also of the molecular mechanisms that lead to the success of the parasitic infection.

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Section: Leishmania Infantum Ntpdasessupporting

confidence: 81%

Section: Leishmania Infantum Ntpdasesmentioning

confidence: 99%

Section: Leishmania Ntpdases Antigenicitymentioning

confidence: 99%

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NTPDase activities: possible roles on Leishmania spp infectivity and virulence

Paes-Vieira

Gomes-Vieira

Meyer‐Fernandes

2018

Cell Biology International

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“…In previous works, polyclonal anti-SmB2LJ antibodies (r175-194, sequence : AALSLTKLINIAETSLPVDV, GenBank accession ABI79456.1) produced by immunization with SmATPDase 2 peptides, as well as antipotato apyrases antibodies, inhibited the activity the S. mansoni ATP diphosphohydrolase isoforms. 22,23,26,27 Additionally, antibodies against peptides derived from Leishmania braziliensis 26 and Leishmania infantum 27 NTPDase 1 reduced ATPase and ADPase activity of this enzyme in these parasites. Here, we show a significant reduction in ATP hydrolysis, suggesting that anti-SmATPDase antibodies could be able to interfere with the catalytic activity of enzymes from macrophages that hydrolyse nucleosides triphosphates, Stimulation of P2X 7 receptors may also play an important role in the generation of multinucleated giant cells (MGCs).…”

Section: Discussionmentioning

confidence: 98%

Antischistosome antibodies change NTPDase 1 activity from macrophages

Marconato

Gusmão

Melo

et al. 2017

Parasite Immunology

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NTPDases are enzymes that hydrolyse diphosphate and triphosphate nucleosides, regulating purinergic signalling in many organisms. The Schistosoma mansoni NTPDases, SmATPDases 1 and 2, are antigenic proteins and display a significant homology with the isoforms found in mammalian cells. In this work, we investigated whether anti-SmATPDase antibodies from S. mansoni-infected mice sera show cross-reactivity with the NTPDase 1 isoform from macrophages and how this event affects the cell proliferation. By Western blot, anti-SmATPDase antibodies present in serum from infected mice recognized 2 bands with approximately 53 and 58 kDa, corresponding to NTPDase 1. Additionally, the enzyme was identified in macrophages by immunofluorescence and the anti-SmATPDase antibodies were able to reduce activity enzyme (22%). Macrophages incubated with commercial polyclonal antibodies reactive with NTPDase 1 (anti-CD39) showed a reduction of 40% of the enzyme activity. In proliferation assays, macrophage proliferation was inhibited 11% and 90% by pooled sera from infected animals and anti-CD39, respectively. The results suggest that inhibition of NTPDase 1 in macrophages by antibodies produced against the isoforms of the S. mansoni ATPDases could be a mechanism of regulation in the immune response during experimental schistosomiasis.

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“…Furthermore, both antibodies were able to inhibit ecto-ATPase activity of L. braziliensis and signifi cantly reduce the promastigotes growth in vitro . Interestingly, the antibody that showed to be more effective in inhibition of ecto-ATPase activity was also more cytotoxic, suggesting that this activity may be involved in cell survival (Porcino et al 2012 ).…”

Section: Molecular Evidences For Occurrence Of E-ntpdasementioning

confidence: 96%

Ecto-nucleotidases and Ecto-phosphatases from Leishmania and Trypanosoma Parasites

Freitas-Mesquita

Meyer‐Fernandes

2013

Subcellular Biochemistry

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Ecto-enzymes can be defined as membrane-bound proteins that have their active site facing the extracellular millieu. In trypanosomatids, the physiological roles of these enzymes remain to be completed elucidated; however, many important events have already been related to them, such as the survival of parasites during their complex life cycle and the successful establishment of host infection. This chapter focuses on two remarkable classes of ecto-enzymes: ecto-nucleotidases and ecto-phosphatases, summarizing their occurrence and possible physiological roles in Leishmania and Trypanosoma genera. Ecto-nucleotidases are characterized by their ability to hydrolyze extracellular nucleotides, playing an important role in purinergic signaling. By the action of these ecto-enzymes, parasites are capable of modulating the host immune system, which leads to a successful parasite infection. Furthermore, ecto-nucleotidases are also involved in the purine salvage pathway, acting in the generation of nucleosides that are able to cross plasma membrane via specialized transporters. Another important ecto-enzyme present in a vast number of pathogenic organisms is the ecto-phosphatase. These enzymes are able to hydrolyze extracellular phosphorylated substrates, releasing free inorganic phosphate that can be internalized by the cell, crossing the plasma membrane through a Pi-transporter. Ecto-phosphatases are also involved in the invasion and survival of parasite in the host cells. Several alternative functions have been suggested for these enzymes in parasites, such as participation in their proliferation, differentiation, nutrition and protection. In this context, the present chapter provides an overview of recent discoveries related to the occurrence of ecto-nucleotidase and ecto-phosphatase activities in Leishmania and Trypanosoma parasites.

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Leishmania (Viannia) braziliensis nucleoside triphosphate diphosphohydrolase (NTPDase 1): Localization and in vitro inhibition of promastigotes growth by polyclonal antibodies

Cited by 16 publications

References 38 publications

NTPDase activities: possible roles on Leishmania spp infectivity and virulence

NTPDase activities: possible roles on Leishmania spp infectivity and virulence

Antischistosome antibodies change NTPDase 1 activity from macrophages

Ecto-nucleotidases and Ecto-phosphatases from Leishmania and Trypanosoma Parasites

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