caa a22 4500 606236775 CHVBK 20210128101249.0 cr unu---uuuuu 210128e20150501xx s 000 0 eng 10.1007/s11010-015-2347-9 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2347-9 Neuroinflammation after neonatal hypoxia-ischemia is associated with alterations in the purinergic system: adenosine deaminase 1 isoenzyme is the most predominant after insult [Elektronische Daten] [Victor Pimentel, Maria Moretto, Mariana Oliveira, Daniela Zanini, Ana Sebastião, Maria Schetinger] Hypoxic-ischemic (HI) injury perinatal brain is a major contributor to morbidity and mortality to infants and children. Adenosine may play a role in the pathophysiology of HI, since it modulates the inflammatory process and the release of several neurotransmitters. Thus, the aim of this study was to identify the isoforms of adenosine deaminase (ADA) responsible for the enzymatic activity as well as the adenosine kinase (ADK) and A1 adenosine receptor (A1R) expression in the cerebral cortex eight days after HI. Myeloperoxidase (MPO) and N-acetyl-glucosaminidase (NAG) were assessed as inflammation markers. ADA activity was analyzed, in the presence or absence of a specific ADA1 inhibitor, erythro-9-(2-hydroxy-3-nonyl) adenine. The ADA1 activity (92.6%) was significantly higher than ADA2 (7.4%) activity in the cerebral cortex eight days after HI. A1Rs and ADK protein expression showed decreased 8days after insult. Interestingly, the ADA1, MPO, and NAG activities were correlated positively. In view of this, we conclude that the inhibitor of ADA1, in in vitro conditions, was effective in decreasing the ADA activity, and that mainly ADA1 isoform is responsible for the increase in the ADA activity 8days after HI insult. Therefore, HI neonatal was able to alter the ADK and A1R expression. Thus, due to the importance of adenosine signaling in the regulation of inflammatory and immune process and the crucial role of ADA in the postischemic homeostase of adenosine as well as during inflammatory process, we suggest that ADA1 inhibitors may play an important role in the regulation of events that follow the HI insult, favoring the increase in the adenosine in the sites of tissue injury. Together, these results highlight a role of the purinergic signaling cascade in the pathophysiology of HI neonatal. Springer Science+Business Media New York, 2015 Hypoxia ischemia nationallicence Cerebral cortex nationallicence Adenosine deaminase nationallicence Isoenzymes nationallicence Adenosine receptors nationallicence Inflammation markers nationallicence HI : Hypoxia-ischemia nationallicence ADA : Adenosine deaminase nationallicence ADK : Adenosine kinase nationallicence A1R : Adenosine A1 receptor nationallicence MPO : Myeloperoxidase nationallicence NAG : N-Acetyl-glucosaminidase nationallicence EHNA : Erythro-9-(2-hydroxy-3-nonyl) adenine nationallicence Pimentel Victor Postgraduate Program in Toxicological Biochemistry, Department of Chemistry, Federal University of Santa Maria, Santa Maria, RS, Brazil aut Moretto Maria Postgraduate Program in Pharmaceutical Science, Department of Clinical Analysis and Toxicology, Federal University of Santa Maria, Santa Maria, RS, Brazil aut Oliveira Mariana Faculty of Medicine, Institute of Pharmacology and Neurosciences, University of Lisbon, Lisbon, Portugal aut Zanini Daniela Postgraduate Program in Toxicological Biochemistry, Department of Chemistry, Federal University of Santa Maria, Santa Maria, RS, Brazil aut Sebastião Ana Faculty of Medicine, Institute of Pharmacology and Neurosciences, University of Lisbon, Lisbon, Portugal aut Schetinger Maria Postgraduate Program in Toxicological Biochemistry, Department of Chemistry, Federal University of Santa Maria, Santa Maria, RS, Brazil aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 403/1-2(2015-05-01), 169-177 0300-8177 403:1-2<169 2015 403 11010 https://doi.org/10.1007/s11010-015-2347-9 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2347-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Pimentel Victor Postgraduate Program in Toxicological Biochemistry, Department of Chemistry, Federal University of Santa Maria, Santa Maria, RS, Brazil aut NATIONALLICENCE 700 1- Moretto Maria Postgraduate Program in Pharmaceutical Science, Department of Clinical Analysis and Toxicology, Federal University of Santa Maria, Santa Maria, RS, Brazil aut NATIONALLICENCE 700 1- Oliveira Mariana Faculty of Medicine, Institute of Pharmacology and Neurosciences, University of Lisbon, Lisbon, Portugal aut NATIONALLICENCE 700 1- Zanini Daniela Postgraduate Program in Toxicological Biochemistry, Department of Chemistry, Federal University of Santa Maria, Santa Maria, RS, Brazil aut NATIONALLICENCE 700 1- Sebastião Ana Faculty of Medicine, Institute of Pharmacology and Neurosciences, University of Lisbon, Lisbon, Portugal aut NATIONALLICENCE 700 1- Schetinger Maria Postgraduate Program in Toxicological Biochemistry, Department of Chemistry, Federal University of Santa Maria, Santa Maria, RS, Brazil aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 403/1-2(2015-05-01), 169-177 0300-8177 403:1-2<169 2015 403 11010