title: Neuroinflammation after neonatal hypoxia-ischemia is associated with alterations in the purinergic system: adenosine deaminase 1 isoenzyme is the most predominant after insult.
abstract: 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 8 days 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 8 days 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.
authors.affiliation: Postgraduate Program in Toxicological Biochemistry, Department of Chemistry, Federal University of Santa Maria, Santa Maria, RS, Brazil, victor.capi@yahoo.com.br.
authors.forename: Victor Camera
authors.initials: VC
authors.lastname: Pimentel
authors.forename: Maria Beatriz
authors.initials: MB
authors.lastname: Moretto
authors.forename: Mariana Colino
authors.initials: MC
authors.lastname: Oliveira
authors.forename: Daniela
authors.initials: D
authors.lastname: Zanini
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Sebastião
authors.forename: Maria Rosa Chitolina
authors.initials: MR
authors.lastname: Schetinger
mesh_terms: D000118:Acetylglucosaminidase / Q000378:metabolism; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000243:Adenosine Deaminase / Q000378:metabolism*; D000248:Adenosine Kinase / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D001921:Brain / Q000473:pathology*; D002540:Cerebral Cortex / Q000201:enzymology / Q000473:pathology; D020925:Hypoxia-Ischemia, Brain / Q000201:enzymology* / Q000473:pathology*; D007249:Inflammation / Q000473:pathology*; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D011687:Purines / Q000378:metabolism*; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D011687:Purines; D043682:Receptor, Adenosine A1; C010192:9-(2-hydroxy-3-nonyl)adenine; D009195:Peroxidase; D000248:Adenosine Kinase; D000118:Acetylglucosaminidase; D000243:Adenosine Deaminase; D000225:Adenine