Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.1.1.148 (Thy1)
 1,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Extracellular adenine nucleotides are considered mediators of inflammation because they modulate functions of neutrophils and platelets. Until now, this role for adenine nucleotides has not been studied in vivo. In particular in the rat kidney, where ATP- and ADPase activity is present in the glomerular basement membrane, studies about the role of nucleotides may increase our understanding of the dynamics of glomerulonephritis (GN). Therefore, we examined effects of adenine derivatives ATP gamma S, ADP beta S and 2chloro-adenosine (2chloro-ADO) in vitro and during anti-Thy1 GN. The in vitro results show that ADP beta S and ATP gamma S are not degraded by glomerular nucleotidases but, on the other hand do stimulate O2- production of peritoneal exudate cells (PEC). In contrast, 2chloro-ADO significantly inhibits O2- production of peritoneal exudate cells. For in vivo studies rats were rendered nephritic by intravenous injection of monoclonal anti-Thy1 IgG (5 mg/kg body weight). Subsequently, rats were treated with saline (group 1, N = 10), 2chloro-ADO (group 2, N = 10), ADP beta S (group 3, N = 10) or ATP gamma S (group 4, N = 10). All analogs (10 mg/kg body weight) were administered both at t = 0 and t = 12 hour. After 24 hours, rats were sacrificed and kidneys were examined histochemically. In an additional group of nephritic rats (N = 5) proteinuria was studied after 2-chloro-ADO treatment. Results show increased intraglomerular platelet aggregation in nephritic rats treated with ADP beta S, whereas 2chloro-ADO inhibits aggregation significantly as compared with nephritic rats receiving saline. The percentage of granulocytes producing O2- is significantly increased in glomeruli after treatment of nephritic rats with ATP gamma S, whereas cell influx itself is not changed. In contrast, 2chloro-ADO inhibits intraglomerular O2- production, which is associated with the complete inhibition of proteinuria in the early phase of anti-Thy1 GN. These data demonstrate significant pro-inflammatory activities of extracellular adenine nucleotides during anti-Thy1 GN suggesting an anti-inflammatory role for glomerular ATP/ADPase, which in concert with 5' nucleotidase converts ATP and ADP to antiinflammatory ADO.
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PMID:Modulation of anti-Thy1 nephritis in the rat by adenine nucleotides. Evidence for an anti-inflammatory role for nucleotidases. 153 30

Oxygen free radical production inhibits ADPase-mediated antithrombotic action. Different forms of experimental glomerulonephritis (GN) are characterized by early glomerular influx of inflammatory cells and thrombus formation. The causal relationship of these inflammatory events is obscure. Previous studies have shown that glomerular ADPase in the rat kidney may function as a potent antithrombotic principle, whereas this enzyme is highly sensitive for oxygen free radicals. To study whether O2- producing inflammatory cells are able to induce intraglomerular thrombosis via impairment of ADPase, we investigated influx of inflammatory cells in relation to glomerular ADPase activity and platelet aggregation in three models of GN. In two of these models (anti-Thy1 and anti-GBM GN) influx of neutrophils and thrombus formation occurs, whereas in anti-FX1A nephritis this aspect of the inflammatory phase is not present. The results show a relationship between influx of oxygen free radical-producing cells, reduction of glomerular ADPase activity and increased platelet aggregation. Moreover, it is shown that impairment of glomerular ADPase and increased platelet aggregation in anti-Thy1 and anti-GBM GN could be reduced by treatment with superoxide dismutase and catalase. The demonstration that activated neutrophils perfused ex vivo in the rat kidney can directly affect glomerular ADPase and antithrombotic potential in an O2- dependent manner, further supports the proposed sequence of events; oxygen free radicals produced by activated neutrophils reduce glomerular ADPase activity, leading to facilitation of thrombus formation.
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PMID:Intraglomerular platelet aggregation and experimental glomerulonephritis. 236 4

Although both ecto-ADPase and prostacyclin (PGI2) inhibit platelets and neutrophils, their action in acute glomerulonephritis is unknown. We tested the PGI2 analog Iloprost and 2chloroadenosine (2Cl-ADO), an analog of adenosine, the end product of nucleotidase activities, during anti-Thy1 nephritis. Rats received anti-Thy1 immunoglobulin G (5 mg/kg body weight, intravenously) and subsequently one subcutaneous injection of either 2Cl-ADO (10 mg/kg body weight; (n = 6) or Iloprost (1 mg/kg body weight; n = 6). Control rats received anti-Thy1 immunoglobulin G with saline (n = 6) or saline alone (n = 6). After 24 hours, kidneys were processed for light-microscopical evaluation. Proteinuria was studied in additional rats. Results showed that both drugs inhibited intraglomerular platelet activation (P < 0.005). 2Cl-ADO also reduced intraglomerular O2- production of neutrophils (P < 0.05), in contrast to Iloprost. Intraglomerular immunoglobulin G deposition, complement activation, neutrophil influx, and myeloperoxidase release were not affected by 2Cl-ADO or Iloprost. However, proteinuria was completely prevented by both drugs. It is concluded that PGI2 and nucleotidases are potentially able to attenuate this form of nephritis by inhibiting platelet activity, whereas nucleotidases also inhibit neutrophil activity in vivo.
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PMID:Attenuation of anti-Thy1 glomerulonephritis in the rat by anti-inflammatory platelet-inhibiting agents. 767 50

It has been demonstrated in anti-Thy1 glomerulonephritis that extracellular adenine nucleotides have a significant pro-inflammatory activity, however, glomerular ATP/ADPase, which in concert with 5'-nucleotidase converts ATP/ADP, and AMP to anti-inflammatory adenosine had an anti-inflammatory role. We have studied distribution of 5'-nucleotidase and divalent cation-activated ATPase in kidney biopsies of 15 patients with glomerulonephritis. The major finding was an overexpression of 5'-nucleotidase in the mesangium of kidney from patients with membranous nephropathy. No change in 5'-nucleotidase expression was observed in other common forms of glomerulonephritis: IgA nephropathy, mesangioproliferative and mesangiocapillary glomerulonephritis. The distribution of Mg(2+)-ATPase in investigated specimens was similar to control distribution. Results obtained in this study indicate increased mesangial expression of 5'-nucleotidase in non-proliferative form of glomerulonephritis consistent to a role of mesangial cells in inflammatory processes.
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PMID:Increased expression of glomerular mesangial cell 5'-nucleotidase in membranous nephropathy. 1218 7