Capiotti Katiucia Marques, Siebel Anna Maria, Kist Luiza Wilges, Bogo Maurício Reis, Bonan Carla Denise, Da Silva Rosane Souza
Laboratório de Neuroquímica e Psicofarmacologia, Departamento de Biologia Celular e Molecular, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681, 90619-900, Porto Alegre, RS, Brazil.
Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), 90035-003, Porto Alegre, RS, Brazil.
Purinergic Signal. 2016 Jun;12(2):211-20. doi: 10.1007/s11302-015-9494-z. Epub 2016 Jan 14.
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 ecto-adenosine 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.
高血糖是糖尿病（DM）诊断的主要特征。一些研究已经证明了糖尿病与神经传递系统功能障碍之间的关系，如嘌呤能系统。在本研究中，我们评估了高血糖斑马鱼脑细胞膜上的细胞外核苷酸水解和腺苷脱氨基活性。在111 mM葡萄糖处理组中观察到ATP、ADP和AMP水解显著降低，在撤糖7天后恢复到正常水平。在111 mM葡萄糖组中观察到胞外腺苷脱氨酶活性显著增加，在撤糖7天后仍保持升高。可溶性腺苷脱氨酶活性在撤糖7天后才显著增加。我们还评估了成年斑马鱼脑中外核苷三磷酸二磷酸水解酶（E-NTPDases）、胞外5'-核苷酸酶、ADA和腺苷受体的基因表达。在111 mM葡萄糖处理组和撤糖组中，成年斑马鱼脑的entpd 2a.1、entpd 2a.2、entpd 3和entpd 8 mRNA水平降低。在111 mM葡萄糖处理组和撤糖组中，腺苷受体（adora 1、adora 2aa、adora 2ab和adora 2b）的基因表达降低。在撤糖组中，ADA（ada 2a.1）的基因表达降低。用作对照的麦芽糖糊精不影响腺苷受体、ADA和E-NTPDases 2、3和8的表达，而胞外5'-核苷酸酶的表达略有增加，E-NTPDases 1降低。这些发现表明，高血糖可能通过涉及渗透效应的机制影响斑马鱼的胞外核苷酸酶和腺苷脱氨酶活性以及基因表达，这表明嘌呤能系统的改变也可能导致糖尿病引起的进行性认知障碍。
