NTPDase and 5′-nucleotidase activities in rats with alloxan-induced diabetes

Lunkes, Gilberto Inácio; Lunkes, Daniéle Sausen; Morsch, Vera Maria; Mazzanti, Cíntia M.; Morsch, André; Miron, Vinícius; Schetinger, Maria Rosa Chitolina

doi:10.1016/j.diabres.2003.11.016

Cited by 84 publications

(57 citation statements)

References 28 publications

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“…Schmatz et al (2009a) [16] showed that extracellular nucleotide hydrolysis was increased in synaptosomes from the cerebral cortex of rats submitted to streptozotocin-induced diabetes. Lunkes et al (2004) and Miron et al (2007) [25,47] also demonstrated an increase on the activities of the enzymes E-NTPDase and ecto-5′-nucleotidase in platelets and synaptosomes from the cerebral cortex of rats with alloxan-induced diabetes. In contrast to these results, our findings showed that hyperglycemia reduces significantly ATP, ADP, and AMP hydrolyses promoted by ENTPDases and ecto-5′-nucleotidase in zebrafish encephalic membranes.…”

Section: Discussionmentioning

confidence: 87%

“…5 Effect of hyperglycemia on adora gene expression pattern in 111 mM glucose and glucose washout group. Data are expressed as mean ± SEM of four independent experiments performed in quadruplicate expression patterns and activity properties [25,53] and might contribute for the regulation of adenosine levels in different manners.…”

Section: Discussionmentioning

confidence: 99%

“…Also, [24] demonstrated that ATP, ADP, and AMP hydrolyses were increased in synaptosomes from STZinduced diabetic rats, and also, Lunkes et al (2004) [25] demonstrated that diabetic rats show an increase in NTPDase and 5′-nucleotidase activities.…”

Section: Introductionmentioning

confidence: 97%

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

Capiotti

Siebel

Kist

et al. 2016

Purinergic Signalling

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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.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

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

Capiotti

Siebel

Kist

et al. 2016

Purinergic Signalling

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“…Recently, we measured the CD39 expression in these groups and found that it was increased by around 25% in diabetic, hypertensive and diabetic/hypertensive subjects (Lunkes et al, unpublished data). Additionally, using an experimental model of type 1 diabetes induced by alloxan in rats, we observed that NTPDase and 5'-nucleotidase activities were increased in platelets [78,89] and synaptosomes [78]. Taken together, these results may indicate that, in diabetic rats, both NTPDase and 5'-nucleotidase from the central nervous system (CNS) and platelets respond similarly with increased activity [78].…”

Section: Role Of Ntpdase1 In Thromboregulationmentioning

confidence: 72%

NTPDase and 5'‐nucleotidase activities in physiological and disease conditions: New perspectives for human health

et al. 2007

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Abstract. Extracellular nucleotides and nucleosides act as signaling molecules involved in a wide spectrum of biological effects. Their levels are controlled by a complex cell surface-located group of enzymes called ectonucleotidases. There are four major families of ectonucleotidases, nucleoside triphosphate diphosphohydrolases (NTPDases/CD39), ectonucleotide pyrophosphatase/phosphodiesterases (E-NPPs), alkaline phosphatases and ecto-5'-nucleotidase. In the last few years, substantial progress has been made toward the molecular identification of members of the ectonucleotidase families and their enzyme structures and functions. In this review, there is an emphasis on the involvement of NTPDase and 5'-nucleotidase activities in disease processes in several tissues and cell types. Brief background information is given about the general characteristics of these enzymes, followed by a discussion of their roles in thromboregulatory events in diabetes, hypertension, hypercholesterolemia and cancer, as well as in pathological conditions where platelets are less responsive, such as in chronic renal failure. In addition, immunomodulation and cell-cell interactions involving these enzymes are considered, as well as ATP and ADP hydrolysis under different clinical conditions related with alterations in the immune system, such as acute lymphoblastic leukemia (ALL), Bchronic lymphocytic leukemia (B-CLL) and infections associated with human immunodeficiency virus (HIV). Finally, changes in ATP, ADP and AMP hydrolysis induced by inborn errors of metabolism, seizures and epilepsy are discussed in order to highlight the importance of these enzymes in the control of neuronal activity in pathological conditions. Despite advances made toward understanding the molecular structure of ectonucleotidases, much more investigation will be necessary to entirely grasp their role in physiological and pathological conditions.

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“…Isolation of platelets Platelet suspensions were prepared in accordance to the method of Lunkes and colaborators [26], with minor modifications. Total blood was collected by cardiac puncture into a flask containing 120 mM sodium citrate as anticoagulant.…”

Section: Glioma Implantationmentioning

confidence: 99%

Overexpression of NTPDase2 in gliomas promotes systemic inflammation and pulmonary injury

Braganhol

Zanin

Bernardi

et al. 2011

Purinergic Signalling

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Gliomas are the most common and devastating type of primary brain tumor. Many non-neoplastic cells, including immune cells, comprise the tumor microenvironment where they create a milieu that appears to dictate cancer development. ATP and the phosphohydrolytic products ADP and adenosine by activating P2 and P1 receptors may participate in these interactions among malignant and immune cells. Purinergic receptor-mediated cell communication is closely regulated by ectonucleotidases, such as by members of the ectonucleoside triphosphate diphosphohydrolase (E-NTPDase) family, which hydrolyze extracellular nucleotides. We have shown that gliomas, unlike astrocytes, exhibit low NTPDase activity.Furthermore, ATP induces glioma cell proliferation and the co-administration of apyrase decreases progression of injected cells in vivo. We have previously shown that NTPDase2 reconstitution dramatically increases tumor growth in vivo. Here we evaluated whether NTPDase2 reconstitution to gliomas modulates systemic inflammatory responses. We observed that NTPDase2 overexpression modulated pro-inflammatory cytokine production and platelet reactivity. Additionally, pathological alterations in the lungs were observed in rats bearing these tumors. Our results suggest that disruption of purinergic signaling via ADP accumulation creates an inflammatory state that may promote tumor spread and dictate clinical progression.

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NTPDase and 5′-nucleotidase activities in rats with alloxan-induced diabetes

Cited by 84 publications

References 28 publications

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

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

NTPDase and 5'‐nucleotidase activities in physiological and disease conditions: New perspectives for human health

Overexpression of NTPDase2 in gliomas promotes systemic inflammation and pulmonary injury

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