Suppression of ATP Diphosphohydrolase/CD39 in Human Vascular Endothelial Cells

Imai, Masato; Kaczmarek, Elżbieta; Koziak, Katarzyna; Sévigny, Jean; Goepfert, Christian; Guckelberger, Olaf; Csizmadia, Eva; Esch, and Jan Schulte am; Robson, Simon C.

doi:10.1021/bi990543p

Cited by 36 publications

(19 citation statements)

References 45 publications

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“…This is presumably because of the systemic antiaggregatory effects of the administered enzyme [Koyamada et al, 1996]. The generation of NTPDase1-deficient mice (cd39 -/-) corroborated the role of NTPDase1 as a chief vascular ectonucleotidase and affirmed its importance in the con-trol of purinergic signaling in both hemostasis and thromboregulation [Enjyoji et al, 1999, Imai et al, 1999aZimmermann, 1999b].…”

Section: Some Functional Cluesmentioning

confidence: 69%

Ectonucleotidases: Some recent developments and a note on nomenclature

Zimmermann

2001

Drug Development Research

372

333

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Extracellular nucleotides such as ATP, ADP, UTP, UDP, and also diadenosine polyphosphates act as signaling molecules and can be inactivated by hydrolysis via ectonucleotidases. A considerable number of surface-located enzymes can potentially be involved in the extracellular hydrolysis pathway. These include the E-NTPDase family (ectonucleoside triphosphate diphosphohydrolase family), the E-NPP family (ectonucleotide pyrophosphatase/phosphodiesterase family), ecto-5′-nucleotidase, and alkaline phosphatases. In addition, activity of ectonucleoside diphosphokinase can interconvert extracellular nucleotides, and ATP can be used as a cosubstrate of ectoprotein kinase in the phosphorylation of surface-located proteins. Members of the various ectonucleotidase families reveal overlapping substrate specificity and tissue distribution whose functional significance needs to be further elucidated. Considerable progress has been made in the past several years in characterizing novel enzyme species and their molecular and functional properties. First knock-out mice reveal insight into physiological processes governed by the activity of specific ectonucleotidases. Together this work has led to a deeper understanding of the pathways of extracellular nucleotide metabolism, including their interplay with P2 and P1 receptors or also other physiological mechanisms. Drug Dev. Res. 52:44-56, 2001.

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Section: Some Functional Cluesmentioning

confidence: 69%

Ectonucleotidases: Some recent developments and a note on nomenclature

Zimmermann

2001

Drug Development Research

372

333

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“…42,43 Endothelial CD39 has been viewed as playing a protective, thromboregulatory role in restricting the size of the hemostatic plug by limiting excessive platelet aggregation. [43][44][45][46] Indeed, excessive platelet accumulation and recruitment can be treated with soluble forms of CD39. 47,48 Moreover, a thromboregulatory role could be demonstrated in a model of stroke or ischemia-reperfusion injury, where damage in cd39-null mice was readily treated with soluble forms of CD39/apyrase.…”

Section: Discussionmentioning

confidence: 99%

Endogenous adenosine produced during hypoxia attenuates neutrophil accumulation: coordination by extracellular nucleotide metabolism

Eltzschig

Thompson

Karhausen

et al. 2004

Blood

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328

323

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Hypoxia is a well-documented inflammatory stimulus and results in tissue polymorphonuclear leukocyte (PMN) accumulation. Likewise, increased tissue adenosine levels are commonly associated with hypoxia, and given the anti-inflammatory properties of adenosine, we hypothesized that adenosine production via adenine nucleotide metabolism at the vascular surface triggers an endogenous anti-inflammatory response during hypoxia. Initial in vitro studies indicated that endogenously generated adenosine, through activation

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“…CD39 RNA stability does not change in activated EC [Enjyoji et al, 1999;Imai et al, 1999b;Koziak et al, 1999] and there is typically reconstitution of mRNA at 24 h (Fig. 2).…”

Section: Transcriptional Regulation Oxidative Damage Proteolytic Dementioning

confidence: 94%

Modulation of extracellular nucleotide‐mediated signaling by CD39/nucleoside triphosphate diphosphohydrolase‐1

Robson

Enjyoji

Goepfert

et al. 2001

Drug Development Research

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Extracellular nucleotide stimulation of purinergic/pyrimidinergic type-2 (P2) receptors are components of platelet, endothelial cell (EC), and leukocyte activation that culminate in vascular thrombosis and inflammation in vivo. CD39, the prototype nucleoside triphosphate diphosphohydrolase (or NTPDase-1), is highly expressed on quiescent endothelium, monocytes, and activated lymphocytes and therefore could influence these pathways. The potential of NTPDase-1 to regulate P2-receptor function in the vasculature has been established by our generation of cd39-null mice. These mice exhibit a prothrombotic vascular phenotype ascribed to overexpression of tissue factor by endothelial cells following aberrant P2-(and potentially adenosine 2a/3) receptor activation. Mutant mice also show perturbations in hemostasis, secondary to platelet P2Y1-receptor desensitization. In addition, administration of soluble NTPDase and/or induction of CD39 overexpression by adenoviral vectors consistently result in amelioration of vascular injury in several animal models tested. CD39 is also the major NTPDase expressed by monocyte-macrophages (Mo). Upregulation of tissue factor expression by Mo in vitro and alterations in splenic populations in vivo have been observed in cd39-null mice. Paradoxical inhibition of integrin-mediated adhesion and transendothelial migration of cd39-null Mo are also related to aberrant P2-receptor activation and have also been observed in vitro and in vivo. Overexpression of CD39 following infection with recombinant adenoviral vectors also blocks LPS-induced ATP secretion and inhibits IL-1 release in vitro. These studies confirm a role for CD39 in the differential regulation of P2-receptor activity and function in platelets, vascular, and immune cells. Drug Dev. Res. 53:193-207, 2001.

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Suppression of ATP Diphosphohydrolase/CD39 in Human Vascular Endothelial Cells

Cited by 36 publications

References 45 publications

Ectonucleotidases: Some recent developments and a note on nomenclature

Ectonucleotidases: Some recent developments and a note on nomenclature

Endogenous adenosine produced during hypoxia attenuates neutrophil accumulation: coordination by extracellular nucleotide metabolism

Modulation of extracellular nucleotide‐mediated signaling by CD39/nucleoside triphosphate diphosphohydrolase‐1

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