Effect of zinc supplementation on E-ADA activity, seric zinc, and cytokines levels of Trypanosoma evansi infected wistar rats

Bottari, Nathieli B.; Baldissera, Matheus D.; Oliveira, Camila Belmonte; Duarte, Thiago; Leal, Marta L.R.; Thomé, Gustavo R.; Zanini, Daniela; Schetinger, Maria Rosa Chitolina; Nunes, Matheus A.G.; Dressler, Valderi L.; Monteiro, Sílvia González; Tonin, Alexandre Alberto; Silva, Aleksandro S. Da

doi:10.1016/j.micpath.2014.06.004

Cited by 8 publications

(3 citation statements)

References 23 publications

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“…The absence of ADA activity causes lymph-toxic deoxyadenosine triphosphate accumulation that results in apoptosis in immature thymocytes ( Buckley, 2004 ; Shaw et al, 2017 ; Turel et al, 2017 ). Different crystal structures of ADA have been obtained, containing a tightly bound Zn 2+ that is essential for the stability and the catalytic function of the native protein ( Wilson et al, 1991 ; Cooper et al, 1997 ; Wang and Quiocho, 1998 ; Kinoshita et al, 2005 ; Niu et al, 2010 ; Khare et al, 2012 ; Bottari et al, 2014 ; Grosskopf et al, 2017 ). ADA is a cytosolic enzyme localized in many human tissues, being the lymphoid system (lymph nodes, spleen and thymus) where the highest levels are found ( Beyazit et al, 2012 ; Maiuolo et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Molecular Evidence of Adenosine Deaminase Linking Adenosine A2A Receptor and CD26 Proteins

Moreno¹,

Canet²,

Gracia³

et al. 2018

Front. Pharmacol.

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Adenosine is an endogenous purine nucleoside that acts in all living systems as a homeostatic network regulator through many pathways, which are adenosine receptor (AR)-dependent and -independent. From a metabolic point of view, adenosine deaminase (ADA) is an essential protein in the regulation of the total intracellular and extracellular adenosine in a tissue. In addition to its cytosolic localization, ADA is also expressed as an ecto-enzyme on the surface of different cells. Dipeptidyl peptidase IV (CD26) and some ARs act as binding proteins for extracellular ADA in humans. Since CD26 and ARs interact with ADA at opposite sites, we have investigated if ADA can function as a cell-to-cell communication molecule by bridging the anchoring molecules CD26 and A2AR present on the surfaces of the interacting cells. By combining site-directed mutagenesis of ADA amino acids involved in binding to A2AR and a modification of the bioluminescence resonance energy transfer (BRET) technique that allows detection of interactions between two proteins expressed in different cell populations with low steric hindrance (NanoBRET), we show direct evidence of the specific formation of trimeric complexes CD26-ADA-A2AR involving two cells. By dynamic mass redistribution assays and ligand binding experiments, we also demonstrate that A2AR-NanoLuc fusion proteins are functional. The existence of this ternary complex is in good agreement with the hypothesis that ADA could bridge T-cells (expressing CD26) and dendritic cells (expressing A2AR). This is a new metabolic function for ecto-ADA that, being a single chain protein, it has been considered as an example of moonlighting protein, because it performs more than one functional role (as a catalyst, a costimulator, an allosteric modulator and a cell-to-cell connector) without partitioning these functions in different subunits.

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Section: Introductionmentioning

confidence: 99%

Molecular Evidence of Adenosine Deaminase Linking Adenosine A2A Receptor and CD26 Proteins

Moreno¹,

Canet²,

Gracia³

et al. 2018

Front. Pharmacol.

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“…Although Zn is an essential micronutrient for bacteria, it is toxic at high concentrations [ 23 ]. Zn plays a protective role against infection by other pathogens, such as shiga-toxigenic Escherichia coli [ 24 ] and Trypanosoma evansi [ 25 ]. A bacteriostatic effect of Zn was demonstrated using in vitro bacterial growth assays.…”

Section: Discussionmentioning

confidence: 99%

Combination of Zinc and All-Trans Retinoic Acid Promotes Protection against Listeria monocytogenes Infection

et al. 2015

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Zinc (Zn) is the second most abundant transition metal after iron. It plays a vital role in living organisms and affects multiple aspects of the immune system. All-trans retinoic acid (atRA) is an isomeric form of the vitamin A or retinol. It possesses the greatest biological activity of Vitamin A. Vitamin A and related retinoids influence many aspects of immunity. In this study, we demonstrated that treatment with a combination of Zn and atRA contributes to host resistance against infection by Listeria monocytogenes. Pretreatment with Zn and atRA enhanced resistance against L. monocytogenes infection in mice and treatment with both Zn and atRA showed a higher protective effect than treatment with either alone. Supplementation with Zn, atRA or their combination decreased the number of L. monocytogenes present in target organs. In vitro, supplementation increased the bacterial uptake by macrophage cells and reduced the replication of L. monocytogenes. Our results suggest that the combination of Zn and atRA has a great bacteriostatic impact on L. monocytogenes and its infection.

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“… 7 Several crystal structures of ADA have been discovered, each featuring a firmly bound Zn 2+ that is crucial for the native protein’s stability and catalytic activity. 8 , 9 A previous study examines the effect of Zn 2+ on the maintenance of ADA. The protein’s crystallographic structure preserved a high degree of order and homology to the original structure when Zn 2+ was removed, with some modifications localized to the regions bordering the pocket.…”

Section: Dear Editormentioning

confidence: 99%

Pregnant and Breastfeeding Mothers Who Have Received the ChAdOx1 AstraZeneca COVID-19 Vaccine May Have Infants with an Increased Risk of Zinc Insufficiency and SCID Disease

2022

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Effect of zinc supplementation on E-ADA activity, seric zinc, and cytokines levels of Trypanosoma evansi infected wistar rats

Cited by 8 publications

References 23 publications

Molecular Evidence of Adenosine Deaminase Linking Adenosine A2A Receptor and CD26 Proteins

Molecular Evidence of Adenosine Deaminase Linking Adenosine A2A Receptor and CD26 Proteins

Combination of Zinc and All-Trans Retinoic Acid Promotes Protection against Listeria monocytogenes Infection

Pregnant and Breastfeeding Mothers Who Have Received the ChAdOx1 AstraZeneca COVID-19 Vaccine May Have Infants with an Increased Risk of Zinc Insufficiency and SCID Disease

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