Disease relevance of CD39

• These results suggest that transgenic expression of human CD39 does not interfere with islet function and may be a useful strategy to inhibit thrombosis induced by intraportal administration of islet xenografts [1].
• We have shown that ATPDase activity is rapidly lost from the surface of the EC following ischemia-reperfusion injury and during xenograft rejection [2].

High impact information on CD39

• Loss of ATP diphosphohydrolase activity with endothelial cell activation [3].
• In contrast, ATPDase/cd39 was detected in vascular endothelium and smooth muscle in these organs [4].
• This ATPDase was localized by immunohistochemistry to the bile canalicular domain of hepatocytes and to the luminal side of the renal ductular epithelium [4].
• Kinetic effects of Ca2+ and Mg2+ on ATP hydrolysis by the purified ATP diphosphohydrolase [5].
• Characterization and purification of a calcium-sensitive ATP diphosphohydrolase from pig pancreas [6].

Biological context of CD39

• Expression of CD39 modestly prolonged graft survival (90.2+/-5.4 hr, mean+/-SD, n=5) when compared with Adbeta-gal-infected grafts (67.4+/-5.4 hr, P<0.005) and perfusion controls (66.4+/-5.2 hr; P<0.005) [7].
• Whether E-NTPDase1/CD39 is localized to cardiac neurons and modulates norepinephrine exocytosis in intact heart tissue remained untested [8].
• CD39 (E-NTPDase1), is the endothelial ecto-ADPase inhibiting platelet function via hydrolysis of released platelet ADP [9].
• Both enzymes exhibited kinetic properties typical for all members of the NTPDase family, e.g. low substrate specificity for tri- and diphosphonucleosides, divalent cations dependency and insensitivity towards ATPase inhibitors [10].
• Thus among the four proteins labeled with 8-N3-ATP on the pancreatic zymogen granule membrane, the 53-kDa integral membrane glycoprotein was shown to bear the catalytic site of the ATP diphosphohydrolase [11].

Anatomical context of CD39

• The complete cDNA of NTPDase1 from aorta endothelial cells was sequenced using primer walking [12].
• Two proteolytic products of NTPDase1, with molecular mass of 54 and 27 kDa, respectively, were consistently present in proteins from transfected COS-7 cells and in particulate fractions from different tissues [12].
• Immunohistological examination of AdCD39-infected grafts confirmed successful CD39 gene transfer into the endocardium and macrovasculature [7].
• By curtailing NE release, in addition to its effects as an antithrombotic agent, soluble CD39 may constitute a novel therapeutic approach to ischemic complications in the myocardium [8].
• This suggests that norepinephrine and ATP are coreleased upon depolarization of cardiac sympathetic nerve endings and that ATP enhances norepinephrine exocytosis by an action modulated by E-NTPDase1/CD39 activity [8].

Associations of CD39 with chemical compounds

• In this study, we have investigated the distribution of the enzyme nucleoside triphosphate diphosphohydrolase-1 (NTPDase1; EC 3.6.1.5) in a subset of pig tissues by biochemical activity and Western blotting with antibodies against porcine NTPDase1 [12].
• Expression of the complete cDNA in COS-7 cells confirmed that NTPDase1 codes for a transmembrane glycoprotein with ecto-ATPase and ecto-ADPase activities [12].
• Importantly, expression of human CD39 in the islets of transgenic mice had no deleterious effect on glucose metabolism [1].
• We report that E-NTPDase1/CD39 is selectively localized in human and porcine cardiac neurons and that depolarization of porcine heart tissue elicits omega-conotoxin-inhibitable release of both norepinephrine and ATP [8].
• Extracellular purine concentrations are, in great part, determined by ectonucleotidases, namely, the ATP diphosphohydrolase, also identified as CD39, a lymphocyte cell surface marker [13].

Analytical, diagnostic and therapeutic context of CD39

• CONCLUSIONS: Recombinant adenoviral infection can induce expression of CD39 within cardiac xenografts and provide survival benefits in vivo [7].
• Nucleoside triphosphate diphosphohydrolase (NTPDase or CD39) is a vascular ectoenzyme that hydrolyses ATP and ADP; however, this activity is lost during reperfusion injury [7].
• INTRODUCTION: This study evaluated CD39 in a porcine model of balloon angioplasty and in plasma of patients undergoing percutaneous intervention [9].
• Two isoforms of ATPDase were found (I and II), corresponding to molecular masses of 78,000 and 54,000, respectively, as estimated by SDS-PAGE [13].
• Particulate fractions, prepared from the different lymphoid organs by ultracentrifugation on a sucrose cushion, showed about a 10-fold enrichment of ATPDase activity [13].

References