Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.2.1.31 (beta-glucuronidase)
7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pluripotent human erythroleukaemia cell line, HEL, possesses erythrocytic, megakaryocytic and macrophage-like properties. With respect to signal transduction, HEL cells have been used as a model system for platelets, but little attention has been paid to their phagocytic properties. We studied the effects of various receptor agonists on the intracellular free Ca2+ concentration ([Ca2+]i) in HEL cells. Thrombin, platelet-activating factor (PAF), ATP, UTP, prostaglandins E1 and E2 (PGE1 and PGE2), the PGE2 analogue sulprostone and the stable PGI2 analogues iloprost and cicaprost increased [Ca2+]i. ADP was less effective than ATP, and UDP was unable to increase [Ca2+]i. The increases in [Ca2+]i induced by thrombin, PAF, ATP, UTP, iloprost and cicaprost were pertussis toxin-insensitive, whereas the increases induced by PGE2 and sulprostone were completely inhibited by the toxin. The increase in [Ca2+]i induced by PGE1 was partially inhibited by pertussis toxin. PGE2 did not desensitize the increase in [Ca2+]i induced by iloprost, and vice versa. PGE1 desensitized the response to PGE2 and iloprost but not vice versa. Adrenaline potentiated the iloprost- but not the PGE2-induced rise in [Ca2+]i. The phorbol ester phorbol 12-myristate 13-acetate completely blocked the rise in [Ca2+]i induced by ATP and PGE1, whereas the increases induced by thrombin and PAF were only partially inhibited. Agonists increased [Ca2+]i through release from internal stores and sustained Ca2+ influx. Thrombin stimulated Mn2+ influx, which was blocked by Ni2+. Diltiazem, isradipine, gramicidin and 1-(beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl)-1H-imidazole hydrochloride (SK&F 96365) did not affect agonist-induced rises in [Ca2+]i. HEL cells contained substantial amounts of beta-glucuronidase which, however, could not be released, and they did not aggregate or generate superoxide. Our data suggest that: (1) HEL cells possess nucleotide receptors with properties similar to those of phagocytes; (2) they possess receptors for PGE2 and PGI2, and PGE1 is an agonist at both receptors; (3) agonist-induced increases in [Ca2+]i are mediated through pertussis toxin-sensitive as well as -insensitive signal transduction pathways; and (4) agonists increase [Ca2+]i by mobilization from internal stores and influx from the extracellular space through cation channels with properties similar to those of phagocytes and platelets.
...
PMID:Receptor-mediated increases in cytosolic Ca2+ in the human erythroleukaemia cell line involve pertussis toxin-sensitive and -insensitive pathways. 131 May 89

In this study the causes of organ damage after cardiopulmonary bypass were multifactorial. The concentration of the proteolytic enzyme elastase, which was released from activated granulocytes in the milieu of significantly reduced levels of alpha 1-protease inhibitor (p less than 0.01), increased during cardiopulmonary bypass (p less than 0.01). In addition, bypass initiated platelet aggregation, which both altered the eicosanoid metabolism and caused the level of thromboxane A2 to increase and surpass the level of prostaglandin I2. Because thromboxane A2 dominance subsided immediately after cardiopulmonary bypass, the effect of thromboxane A2 (vasoconstriction) on the development of organ damage may have been influential only during bypass. Both during and after bypass, the increase in endothelin excretion (p less than 0.01 to 0.05) was believed to induce a further vasoconstriction in the microvasculature. On completion of the cardiopulmonary bypass, the elevation of the lysosomal enzyme beta-glucuronidase, which is a sensitive indicator of cellular damage, was influenced by the concentrations of elastase (r = 0.8) and endothelin (r = 0.52). As evidenced by leuko-sequestration in the lung after cardiopulmonary bypass, the increase in the alveolar-arterial oxygen tension difference correlated with the elastase concentration (r = 0.68). Renal damage, which was detected by an increase in renal tubular enzymes (N-acetyl-beta-D-glucosaminidase and gamma-glutamyltranspeptidase) was affected by the endothelin (r = 0.68, 0.56) and elastase levels (r = 0.58, 0.68), respectively, but not by the ratio of thromboxane B2 to prostaglandin F1 alpha. The elastase level influenced the pulmonary vascular resistance (r = 0.56). However, neither the cardiac index nor the systemic and pulmonary vascular resistances were influenced by the endothelin level and the ratio of thromboxane B2 to prostaglandin F1 alpha.
...
PMID:Evidence of organ damage after cardiopulmonary bypass. The role of elastase and vasoactive mediators. 135 50

The causes of organ failure following cardiopulmonary bypass (CPB) were multi-factorial. Damage was initiated by elastase which was released from activated granulocytes under conditions of significant reduction in the protease inhibitor level (p less than 0.01). Platelet aggregation, initiated by the CPB, altered the eicosanoid metabolism. As a result, the level of thromboxane A2 increased and became dominant in relation to prostaglandin I2. The increase in endothelin excretion observed during and after the CPB induced a further vasoconstrictive response in the microvasculature and accelerated ischemic cellular damage. Upon completion of the CPB, the elevation of the lysosomal enzyme beta-glucuronidase was influenced by the concentration of elastase (r = 0.78). The endothelin level correlated slightly with the elastase level (r = 0.4) during the CPB. This might indicate that there was an interaction between the activated granulocytes and endothelin production. The increase in the alveolar-arterial oxygen tension difference (Aa-DO2) only correlated with the elastase concentration (r = 0.55). Renal damage, which was detected by an increase in renal tubular enzymes (N-acetyl-beta-D-glucosaminidase and gamma-glutamyltranspeptidase), was affected by endothelin (r = 0.68, 0.58) and elastase (r = 0.61, 0.51) respectively, but not by thromboxane B2. Even after the CPB, damage was thought to be perpetuated by the continuous elevation of elastase and endothelin. Since thromboxane A2 dominance subsided immediately after the cardiopulmonary bypass, the effect of thromboxane A2 on the development of organ failure was possibly only influential during the CPB. The cardiac index demonstrated a negative correlation with endothelin (r = -0.69) and a positive correlation with the ratio of TxB2/PGF1 (r = 0.51).(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:[Mechanisms of organ failure following cardiopulmonary bypass--preventive effects of ulinastatin]. 177 3

NO-donor SIN-1 (0.01-1.0 mM) dose-dependently inhibited the basal and FMLP (30.0 mM)-stimulated release of beta-glucuronidase from rat peritoneal leukocytes and antigen-specific stimulation of Interleukin-2 production by T-hybridomas. I-123 LDL binding to human lymphocytes was inhibited by Iloprost (1 mM) but activated by SIN-1 (0.3 mM). We conclude that beside the smooth muscle cells and platelets the blood inflammatory/immune cells are under the PGI2/NO control, however, the precise regulation as well as physiological importance need further investigation.
...
PMID:Influence of no-donor (SIN-1) on functions of inflammatory cells. 205 67

The action of PGE1, PGE2, PGI2 and iloprost on superoxide anion generation, lysosomal enzyme release, and changes of Ca2+ fluxes in human polymorphonuclear leukocytes (PMN) was studied in vitro. Both PGE-type compounds were equipotent inhibitors of FMLP-and PAF-stimulated superoxide anion generation, beta-glucuronidase release (IC50 3-5 mumol/l) and Ca2+ influx while PGI2 and iloprost were ineffective at concentrations up to 10 mumol/l. These inhibitory actions of PGE1 and PGE2 were paralleled by an increase in cAMP level of the PMN while no change occurred with PGI2 and iloprost. None of the prostaglandins affected the initial intracellular Ca2+ liberation after challenge with FMLP or PAF. Preincubation of PMN with PGE1 and PGE2 but not with iloprost resulted in subsequent desensitization against a second administration of these compounds. None of the compounds affected PMN activation produced by arachidonic acid or calcimycin (A 23187). These data demonstrate that PGE-type compounds are effective inhibitors of receptor-mediated (PAF, FMLP) activation of human PMN while prostacyclins are considerably less potent. This suggests that the inhibitory prostaglandin receptor on human PMN belongs to the E-type being functionally different from the inhibitory prostaglandin receptor on human platelets. These results suggest that compounds, such as PGE1 and PGE2 might be superior to prostacyclins to prevent PMN-associated generation of reactive oxygen species and lysosomal enzyme release in situations with endogenous PMN activation, i.e. inflammatory reactions.
...
PMID:Cytotoxic enzyme release and oxygen centered radical formation in human neutrophils are selectively inhibited by E-type prostaglandins but not by PGI2. 215 12

Leakage of lysosomal enzymes is associated with irreversible cellular damage. To determine the effect of prostaglandin I2 analogue and propranolol on the ischaemic myocardium in relation to changes in lysosomal integrity 26 anaesthetised mongrel dogs were divided into three treatment groups and subjected to 2 h coronary occlusion. In the control group (n = 12) physiological saline was infused throughout the experiment. In the prostaglandin I2 analogue group (n = 7) the prostaglandin I2 analogue, OP-41483-alpha-CD;5(E)-6-Deoxa-6,9 alpha-methylene-15-cyclopentyl-16,17,18,19,20-pentanor-PGI2. alpha-cyclodextrin clathrate (5 ng.kg-1.min-1) was infused from 25 min before occlusion until the end of the experiment. In the propranolol group (n = 7) propranolol (0.3 mg.kg-1) was injected for 10 min 25 min before occlusion. Two hours after occlusion mitochondria were prepared from both ischaemic and non-ischaemic areas in each group and their function measured polarographically with succinate as substrate. Fractionation of myocardial tissue from both non-ischaemic and ischaemic areas was performed and the activities of lysosomal enzymes (N-acetyl-beta-glucosaminidase; beta-glucuronidase) were measured. In the control group, mitochondrial function in the ischaemic area was reduced compared with that from the non-ischaemic area. The activities of both lysosomal enzymes were increased significantly in the supernatant fraction obtained from the ischaemic area compared with those for the supernatant from the non-ischaemic area. The administration of prostaglandin I2 analogue or propranolol not only prevented the leakage of lysosomal enzymes but also maintained mitochondrial function.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Prostaglandin I2 analogue and propranolol prevent ischaemia induced mitochondrial dysfunction through the stabilisation of lysosomal membranes. 304 92

In acute pancreatitis, damage to the liver is an important aspect of multiorgan failure. In 28 dogs (20 with bile-trypsin induced acute experimental pancreatitis (AEP], 'total' and 'free' activity of lysosomal hydrolases: beta-glucuronidase, cathepsins and acid phosphatase in mitochondrial and lysosomal subfraction of the liver were determined 12 h or 24 h after the induction of AEP. The respiratory control ratio with sodium succinate as a substrate, using Clarck's electrode and uncoupler-dependent ATP-ase activity in mitochondrial subfraction, was assayed. Groups of dogs were treated or pretreated with prostacyclin (PGI2), 20 ng.kg-1.min-1 i.v. for 12 or 13 h. The relative free activity of hydrolases was significantly elevated in untreated AEP after 12 h and was partially normalized in AEP after 24 h or after 12 h followed by treatment and pretreatment with PGI2. Respiratory control ratio was twice lower than normal in AEP after 12 h and partially normalized after 24 h post PGI2 treatment. The relative free activity of lysosomal hydrolases was highly negatively correlated with respiratory control ratio. It was concluded, that during AEP in dogs the function of liver mitochondria and lysosomal stability are impaired. The significant correlation found between the mitochondrial and lysosomal lesions points to lysosomal-mitochondrial interactions in liver damage in AEP. Prostacyclin in the investigated dose partially prevents the mitochondrial and lysosomal lesions in liver in this disease.
...
PMID:Lysosomal-mitochondrial interrelationships in damage to the liver in acute experimental pancreatitis in dogs. Treatment with prostacyclin (PGI2). 304 48

Previous studies have suggested that increased alpha adrenergic activity stimulated prostaglandin synthesis and may be involved in the modulation of eicosanoid metabolism. These observations prompted investigation of the effect of the alpha adrenergic receptor antagonist phenoxybenzamine and the cyclo-oxygenase inhibitor indomethacin on endotoxin-induced shock severity, and on plasma immunoreactive iTxB2 and i6-keto-PGF1 alpha, the stable metabolites of TxA2 and PGI2, respectively. Pretreatment with indomethacin alone blunted the endotoxin- (8 mg/kg) induced hypoglycemia. Phenoxybenzamine pretreatment also blunted endotoxin-induced mortality (LD80), hypoglycemia, hemoconcentration, and decreased plasma beta-glucuronidase (BG). The combination of phenoxybenzamine and indomethacin resulted in the improvement of all indices of shock severity. Rats pretreated with phenoxybenzamine and indomethacin alone or conjointly also exhibited significantly (P less than 0.05) enhanced survival compared to that of shocked control rats. Percent survival at 48 hr was 24, 64, 80, and 92 in untreated, indomethacin, phenoxybenzamine, and indomethacin + phenoxybenzamine treated, respectively. Mean plasma iTxB2 values at 30 min postendotoxin (15 mg/kg i.v.) were 1,532 +/- 319 pg/ml (N = 10). Phenoxybenzamine pretreatment decreased iTxB2 to 719 +/- 114 pg/ml (N = 10). Phenoxybenzamine pretreatment decreased iTxB2 to 719 +/- 114 pg/ml (N = 10) (P less than 0.05). Plasma i6-keto-PGF1 alpha was increased 4 hr after endotoxin in shocked controls to 4,161 +/- 885 pg/ml (N = 5) and attenuated by phenoxybenzamine to a value of 1,184 +/- 363 pg/ml (N = 4) (P less than 0.05). The results suggest that increased alpha adrenergic activity may be an important stimulus for arachidonic acid metabolism during endotoxemia.
...
PMID:The effects of alpha adrenergic blockade on arachidonic acid metabolism and shock sequelae in endotoxemia. 309 91

The effect of copper on the release of cyclooxygenase metabolites from starch elicited, rat, peritoneal macrophages was investigated. Copper sulphate, in the range 10(-6)-10(-5) M, inhibited the formation of prostaglandin (PG) E2 and thromboxane (Tx) B2, the stable metabolite of TxA2, in a dose dependent manner but had no effect on the production of 6-keto-PGF1 alpha, the stable product of prostacyclin. At higher concentrations (5 x 10(-5) and 10(-4) M) the synthesis of all three metabolites of arachidonic acid (AA) was stimulated as was the release of radioactivity from macrophages prelabelled with 14C AA. Copper had no effect on the metabolism of exogenous AA however. At 10(-4) M copper also stimulated secretion of the lysosomal enzyme, beta-glucuronidase (GUR). Copper nitrate (10(-4) M), but not zinc sulphate, also stimulated eicosanoid formation and lysosomal enzyme release. Our results are consistent with the idea that copper stimulates eicosanoid formation via an effect on PL activity.
...
PMID:Copper modulation of macrophage cyclooxygenase metabolite synthesis. 312 17

The effect of a new prostacyclin analogue OP-41483 on ischemic colonic anastomosis was investigated in dogs. Colonic ischemia was produced by devascularization of the marginal vessels in the left colon and graded into three degrees by measuring colonic blood flow with a hydrogen gas clearance method. The agent was administered intravenously after devascularization using a continuous infusion pump. The parameters studied were colonic blood flow in the submucosal layer, rate of anastomotic leakage, beta-glucuronidase activity and protein content of the colonic mucosa, and histologic changes. After administration of the agent, blood flow increased significantly and beta-glucuronidase activity at the anastomotic site was well preserved at a relatively high level in spite of ischemic change. The anastomotic leakage rate was significantly decreased. The present study proved that administration of this new prostacyclin analogue minimizes ischemic damage, and may be of considerable importance in ischemic colonic anastomoses.
...
PMID:Effect of a new prostacyclin analogue on anastomosis of ischemic colon in dogs. 329 62


1 2 Next >>

---