Hyperglycemia alters E-NTPDases, ecto-5′-nucleotidase, and ectosolic and cytosolic adenosine deaminase activities and expression from encephala of adult zebrafish (Danio rerio)

Abstract

Hyperglycemia is the main feature for the diagnosis of diabetes mellitus (DM). Some studies have demonstrated the relationship between DM and dysfunction on neurotransmission systems, such as the purinergic system. In this study, we evaluated the extracellular nucleotide hydrolysis and adenosine deamination activities from encephalic membranes of hyperglycemic zebrafish. A significant decrease in ATP, ADP, and AMP hydrolyses was observed at 111-mM glucose-treated group, which returned to normal levels after 7 days of glucose withdrawal. A significant increase in ectoadenosine deaminase activity was observed in 111-mM glucose group, which remain elevated after 7 days of glucose withdrawal. The soluble-adenosine deaminase activity was significantly increased just after 7 days of glucose withdrawal. We also evaluated the gene expressions of ecto-nucleoside triphosphate diphosphohydrolases (E-NTPDases), ecto-5′-nucleotidase, ADA, and adenosine receptors from encephala of adult zebrafish. The entpd 2a.1, entpd 2a.2, entpd 3, and entpd 8 mRNA levels from encephala of adult zebrafish were decreased in 111-mM glucose-treated and glucose withdrawal groups. The gene expressions of adenosine receptors (adora 1 , adora 2aa , adora 2ab , and adora 2b ) were decreased in 111-mM glucose-treated and glucose withdrawal groups. The gene expression of ADA (ada 2a.1) was decreased in glucose withdrawal group. Maltodextrin, used as a control, did not affect the expression of adenosine receptors, ADA and E-NTPDases 2, 3, and 8, while the expression of ecto-5′-nucleotidase was slightly increased and the E-NTPDases 1 decreased. These findings demonstrated that hyperglycemia might affect the ecto-nucleotidase and adenosine deaminase activities and gene expression in zebrafish, probably through a mechanism involving the osmotic effect, suggesting that the modifications caused on purinergic system may also contribute to the diabetes-induced progressive cognitive impairment.

Increased ATP and ADO Overflow From Sympathetic Nerve Endings and Mesentery Endothelial Cells Plus Reduced Nitric Oxide Are Involved in Diabetic Neurovascular Dysfunction

“…The increase in the ATP concentration in the extracellular space depends on its release and/or its degradation rate, both mechanisms may operate concurrently. The increase in the basal ATP level and that induced by stimulation is an indication that the extracellular degradation of ATP/ADP was reduced, as was reported by Costa et al (2009) , in rat retinal cell cultures in high glucose, or in encephalic membranes from hyperglycemic zebrafish ( Capiotti et al, 2016 ). In addition, we infer that the diabetes-increased ATP released was similar to that reported in platelets from diabetic patients stimulated with thrombin ( Michno et al, 2007 ).…”

“…(c) Reduced ADO metabolism by ADO deaminase also favors increased ADO levels. Encephalic membranes from hyperglycemic zebrafish exhibit a reduced expression of ADO deaminase ( Capiotti et al, 2016 ), a finding that could be relevant to the current results.…”

Expressional Localization and Functionally Identifying an RNA Editing Enzyme BmADARa of the Silkworm Bombyx mori

“…ADA hydrolyzes adenosine as a neuromodulator to inosine in a manner similar to ADAR catalyzing the water-free amino reaction on dsRNA substrates [35]. Some reports have shown that ADA plays a very important role in the transmission of adenosine signals from the central nervous system, the immune response to inflammation and the diagnosis of diseases in the humans and Drosophila melanogaster [22,36,37]. However, there are few reports on the ADA activity of ADAR.…”

“…A variety of in vitro and mutant experimental evidence indicates that ADARs recognize the specific A site and deaminate through the secondary structure formed by the dsRNA substrate, and the precise location of the editing site in the substrate and the degree of editing are determined by the substrate itself [22,37,39]. Although the secondary structure is determined, until now it has not been possible to predict which A is the target site for ADAR editing based on the secondary structure of RNA.…”

The promise of zebrafish as a model of metabolic syndrome

“…This protein is situated in the myoneural intersection and separates acetylcholine and different esters. Acetylcholinesterase alteration in diabetes can cause certain neurological maladies [7]. A similar convention was employed by Alvarez et al [1], who examined the impact of hyperglycaemia and its relation to retinopathy.…”