Disease relevance of Entpd2

• Loss of NTPDase2 may mediate the bile ductular proliferation typical of obstructive cholestasis [1].
• AIMS: The aim of this study was to assess the effect of experimental rat and disease-mediated human biliary cirrhosis on NTPDase2 expression in the liver [2].
• Conversely, in non-biliary cirrhosis, NTPDase2 is shifted from the portal area to bridging fibrous bands [2].
• Elucidations of the mechanisms regulating NTPDase2 expression may lead to new therapeutic approaches to fibrotic liver disease [2].
• In human biopsy specimens, NTPDase2 expression was lost in cirrhosis owing to primary biliary cirrhosis, whereas NTPDase2 expression was shifted to bridging fibrous bands in cirrhosis owing to hepatitis C [2].

High impact information on Entpd2

• In contrast, decreasing CO(2) levels reduced extracellular adenosine concentration and increased neuronal excitability via adenosine A(1) receptors, ATP receptors, and ecto-ATPase [3].
• METHODS: Bile acid transport activity and ecto-ATPase expression were analyzed in primary rat hepatocytes, rat hepatoma HTC cells, and specially adapted HTC (HTC-R) cells using plasma membrane vesicles and Northern blot, slot blot, ribonuclease protection assay, and Western blot analyses [4].
• In contrast to Mrp2, protein expression of ecto-ATPase and P-gp remained unchanged in endotoxin- and ethinylestradiol-treated animals, whereas P-gp levels increased after CBDL (P < 0.05) [5].
• Hepatic expression of NTPDase2 was determined and contrasted to NTPDase1 using confocal immunofluorescence, immunoelectron microscopy, reverse-transcription polymerase chain reaction, Northern blot analysis, Western blot analysis, and functional assays [6].
• Functional and molecular expression of NTPDase2 was shown in portal fibroblasts near basolateral membranes of bile duct epithelia [6].

Chemical compound and disease context of Entpd2

• Thus, significant changes in liver ecto-ATPase were apparent in 17alpha-ethinylestradiol-induced cholestasis that were opposite to those observed in obstructive cholestasis [7].
• Changes in liver ecto-ATPase in estrogen-induced cholestasis were examined in male rats receiving 17alpha-ethinylestradiol (E groups) for 1, 3, or 5 days (5 mg/kg/day, sc) and compared with changes in rats subjected to obstructive cholestasis (O groups) for 1, 3, or 8 days [7].
• Reduced cortical ecto-ATPase activity in rat brains during prolonged status epilepticus induced by sequential administration of lithium and pilocarpine [8].

Biological context of Entpd2

• Enzymes that can be involved in the extracellular hydrolysis chain are ecto-ATP diphosphohydrolase (ecto-apyrase), ecto-ATPase, ecto-ADPase and 5'-nucleotidase [9].
• NTPDase2 overexpression in portal myofibroblasts isolated from bile duct-ligated rats was achieved by cDNA transfection [1].
• Semi-quantitative immunohistochemistry in the cochlea exposed to 110 dB SPL localized the increased NTPDase1 and NTPDase2 immunostaining in the stria vascularis and up-regulation of NTPDase2 in the intraganglionic spiral bundle [10].
• Evidence for alternative splicing of ecto-ATPase associated with termination of purinergic transmission [11].
• In contrast to NTPDase1, substrate specificity of NTPDase2 was altered with prolonged expression time, resulting in a decrease in the ATPase/ADPase activity ratio from 10 : 1 to 2.5 : 1 [12].

Anatomical context of Entpd2

• NTPDase2 was absent from perisynaptic Schwann cells but was associated with fibroblasts covering the endplate at some distance [13].
• With the onset of myelination, NTPDase2 immunoreactivity remained associated solely with nonmyelinating Schwann cells [13].
• Association of the ecto-ATPase NTPDase2 with glial cells of the peripheral nervous system [13].
• In addition, NTPDase2 immunoreactivity was associated with the satellite glial cells in dorsal root ganglia and sympathetic ganglia, and with the enteric glia surrounding the cell bodies of ganglionic neurons of the myenteric and the submucous plexus [13].
• Using enzyme histochemistry and immunostaining, we demonstrate that NTPDase2 is associated with nonmyelinating Schwann cells of the rat sciatic nerve, whereas NTPDase1 is restricted to blood vessel walls [13].

Associations of Entpd2 with chemical compounds

• The ecto-nucleoside triphosphate diphosphohydrolase NTPDase2/CD39L1 is expressed in a novel functional compartment within the liver [6].
• 5. These results suggest that thyroid hormones could be involved in the regulation of ectonucleotidase activities, such as ecto-ATP diphosphohydrolase and ecto-ATPase, possibly exerting a modulatory role in extracellular adenosine levels [14].
• NTPDase1 preferentially occurred as a dimer that could be dissociated into monomeric forms in the presence of Coomassie Brilliant blue G-250 and dithiothreitol whereas NTPDase2 revealed higher oligomeric forms up to tetramers, largely resistant to dithiothreitol [12].
• In contrast, dibutyryl-cyclic adenosine monophosphate (cAMP) increased ecto-ATPase in both Sertoli and peritubular cells [15].
• As revealed by application of blue native PAGE and a comparison of glutaraldehyde cross-linking, native NTPDase1 and NTPDase2 occur in oligomeric form [12].

Regulatory relationships of Entpd2

• As revealed by Northern analysis of rat tissues, the ecto-ATPase is co-expressed with ecto-ATP diphosphohydrolase in heart, kidney, spleen, thymus, lung, skeletal muscle and brain [9].

Other interactions of Entpd2

• An ecto-ATPase and an ecto-ATP diphosphohydrolase are expressed in rat brain [9].
• Using immunostaining, in situ hybridization and enzyme histochemistry, we demonstrate that the ecto-ATPase nucleoside triphosphate diphosphohydrolase 2 (NTPDase2) is expressed in the subventricular zone and the rostral migratory stream of the adult rat brain [16].
• Double labelling for the astrocyte intermediate filament protein GFAP and the glial glutamate transporter GLAST identifies the NTPDase2-positive cells as type-B cells [16].

Analytical, diagnostic and therapeutic context of Entpd2

• NTPDase2 expression was assessed by immunofluorescence and quantitative real-time reverse transcription PCR [1].
• This study characterized the effect of noise exposure on regulation of NTPDase1 and NTPDase2 expression in the cochlea using a combination of real-time RT-PCR, immunohistochemistry and functional studies [10].
• However, the fate of NTPDase2 after bile duct ligation (BDL) is unknown [2].
• 7. The purified Ca2+/Mg2+ ecto-ATPase from the rat heart sarcolemmal appeared as a single band with MW approximately 90 kD in the SDS-PAGE [17].
• Plasma protein leakage after 100KF perfusion is associated with a significant loss of GPA (57.3 +/- 27.5 vs. 98.4 +/-12.0, p < or = 0.01) and significant decrease of glomerular ecto-ATPase expression (28.7 +/- 11.5 vs. 79.5 +/- 15.0, p < or = 0.001) [18].

References