Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although corticosteroids have been shown to stabilize lysosomal membranes and prevent release of hydrolytic enzymes, the mechanism of membrane stabilization remains obscure. The few reports regarding the use of steroids in myocardial ischemia have been conflicting. This study was undertaken to determine if a pharmacologic dose of the glucocorticoid methylprednisolone would protect the heart during ischemic cardiac arrest. A randomized double-blind study was performed in 25 dogs. Biochemical and hemodynamic parameters were assessed during and after cardiopulmonary bypass and after 30 minutes of ischemic cardiac arrest. Animals were divided into two groups. Group I served as controls and consisted of dogs injected intravenously with the vehicle of methylprednisolone 18 hours and 1 hour prior to experiment. Group II comprised dogs injected with methylprednisolone, 30 mg. per kilogram, IV, at the same time periods. Blood pH, gases, and electrolytes were measured; aortic, left atrial, and left ventricular pressures were monitored; the first derivative of the left ventricular pressure (dp/dt max.) was also determined. Arterial and coronary sinus blood samples were assayed for lactate levels and activity of the lysosomal enzyme, beta-glucuronidase. Left ventricular muscle was assayed for the nucleotides cyclic adenosine 3',5' monophosphate (AMP) and cyclic guanosine 3',5' monophosphate (GMP). Following restoration of coronary flow, mean aortic and left ventricular systolic pressures and left ventricular contractility as determined by dp/dt max. and dp/dt max./IP were depressed in both groups as expected but were significantly higher in Group II than in Group I (p less than 0.05). An increase in levels of both cyclic nucleotides occurred in each group during ischemia, but this increase in cyclic GMP was significantly greater in Group I (p less than 0.05). beta-glucuronidase activity and myocardial potassium loss as determined in coronary sinus blood were both significantly greater in Group I than in Group II (p less than 0.05). Results of this study demonstrate that pretreatment with a pharmacologic dose of methylprednisolone significantly enhances cardiac recovery after ischemia. Lysosomal membrane stability and modulation of cyclic GMP levels may be critical determinants in the mechanism of cardiac ischemia.
J Thorac Cardiovasc Surg 1975 Dec
PMID:Protective effect of methylprednisolone on the heart during ischemic arrest. 17 23

N-acetyl-beta-glucosaminidase (EC 3.2.1.30, recommended name beta-N-Acetylglucosaminidase) was found to be a constituent of human cardiac lysosomes. beta-glucuronidase was also found in this tissue, while lysozyme, an enzyme present in leucocyte lysosomes, was not detectable in the heart. The activities of both N-acetyl-beta-glucosaminidase and beta-glucuronidase were elevated in plasma during the first 24 h after the onset of chest pain in patients with acute myocardial infarction and the peak levels of N-acetyl-beta-glucosaminidase correlated well with those of creatine kinase. N-acetyl-beta-glucosaminidase showed a further rise in plasma activity which gave a peak at 72 h after the onset of chest pain and this was accompanied by a rise in lysozyme activity. It is suggested that lysosome disruption caused by myocardial cell necrosis was responsible for the initial rise in plasma lysosomal enzyme activity and that the subsequent inflammatory reaction gave rise to the second peak.
Cardiovasc Res 1978 Feb
PMID:Plasma lysosomal enzyme activity in acute myocardial infarction. 64 16

The effects of vasodilator therapy upon organ blood flow, beta-glucuronidase activity in plasma and pulmonary surfactant were evaluated before and during cardiopulmonary bypass. Alpha adrenergic blockade with phenoxybenzamine increased the organ blood flow in the heart, brain, stomach, small intestine, large intestine, and liver, whereas it decreased the organ blood flow in the kidney, spleen, and lung. These changes were extremely similar to those observed at hemorrhagic shock. With 2 mg/kg of POB the organ blood flow tended to approach to control levels. The increase of beta-glucuronidase activity at hemorrhagic shock was considerably inhibited after intravenous drip of 2 mg/kg of phenoxybenzamine. We examined the changes of pulmonary surfactant biochemically. Pulmonary surfactant was decreased in endotoxin shock and similar changes were observed in cardiopulmonary bypass when perfusion time was extended to 3 hours. The decrease of pulmonary surfactant after bypass was inhibited by application of POB. From these results, we supposed that the circulatory dynamics during cardiopulmonary bypass might be similar to that of shock and the application of POB in cardiopulmonary bypass might be useful. We applied POB clinically and had good results.
J Cardiovasc Surg (Torino)
PMID:The application of phenoxybenzamine in open heart surgery using cardiopulmonary bypass. 94 23

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.
J Thorac Cardiovasc Surg 1992 Sep
PMID:Evidence of organ damage after cardiopulmonary bypass. The role of elastase and vasoactive mediators. 135 50

The benefit of thrombolytic agents to reduce myocardial infarct size, improve left ventricular (LV) function, and prolong survival in human subjects is generally recognized, although the precise mechanism is poorly defined. This study was designed to evaluate the cardioprotective effects of streptokinase (SK) in rats, a species less responsive to plasminogen activators, using a model of mechanical occlusion and release of the left coronary artery. Myocardial injury and polymorphonuclear leukocyte (PMN) infiltration were determined by measuring creatine phosphokinase (CPK) specific activity and myeloperoxidase (MPO) activity, respectively, in the LV free wall (LVFW). After coronary artery occlusion for 0.5 h and reperfusion for 24 h (myocardial ischemia, MI/R), CPK specific activity decreased from 7.0 +/- 0.3 U/mg protein in the sham + vehicle group to 5.6 +/- 0.5 U/mg protein in the MI/R + vehicle group (n = 19, p less than 0.01), while MPO activity increased from 0.14 +/- 0.03 U/g tissue in the sham + vehicle group to 2.8 +/- 0.7 U/g in the MI/R + vehicle group (p less than 0.001). Administration of SK (100,000 IU/kg + 50,000 IU/kg/h for 2 h beginning 15 min before coronary artery reperfusion) reduced the loss of CPK specific activity from reperfused myocardium (6.8 +/- 0.5 U/mg protein, n = 23, p less than 0.05 as compared with the MI/R + vehicle group) and attenuated the increase in MPO activity (1.3 +/- 0.4 U/g tissue, p less than 0.05 as compared with the MI/R + vehicle group). This dose of SK did not change plasma fibrinogen concentration, slightly reduced plasminogen activity (i.e., 20% from control value), and markedly reduced alpha 2-antiplasmin activity (i.e., 60% from control values). A lower dose of SK (i.e., 10,000 IU/kg + 5,000 IU/kg/h for 2 h) did not reduce myocardial injury, did not attenuate the increase in MPO activity, and had no effect on the measured hemostatic parameters. Survival in all MI/R groups ranged from 62 to 66%, and there were no differences in survival between any of the groups (p greater than 0.05). In a model of arachidonic acid-induced rat hindpaw inflammation, SK had no effect on the increase in MPO activity, suggesting that the increase in myocardial MPO activity was not due to a direct effect on inflammatory cell accumulation. In in vitro studies, SK (1-1,000 U/ml) did not scavenge superoxide anion produced by purine (10 mM) and xanthine oxidase (10 mU/ml), nor did it reduce superoxide release, beta-glucuronidase release, or neutrophil aggregation of rabbit peritoneal neutrophils activated with fMLP.(ABSTRACT TRUNCATED AT 400 WORDS)
J Cardiovasc Pharmacol 1991 Nov
PMID:Reduction in myocardial ischemic/reperfusion injury and neutrophil accumulation after therapeutic administration of streptokinase. 172 70

To clarify the mechanism of irreversible myocardial damage, we studied the relationship between ischaemic mitochondrial dysfunction and leakage of lysosomal enzymes, and the effects of propranolol on myocardial damage. Open chest anaesthetised dogs were divided into six groups: 30 min occlusion of the left anterior coronary artery (LAD); 2 h LAD occlusion; 2 h LAD occlusion after premedication with 0.3 mg.kg-1 propranolol; 30 min LAD occlusion/l h reperfusion; 2 h LAD occlusion/l h reperfusion; and 2 h LAD occlusion/l h reperfusion after propranolol premedication. After occlusion or reperfusion, heart mitochondria were prepared from normal and occluded or reperfused areas, and mitochondrial function (rate of oxygen consumption in State III, and respiratory control index) was measured polarographically. Myocardial tissue was fractionated and activities of lysosomal enzymes (N-acetyl-beta-glucosaminidase and beta-glucuronidase) were measured. Electron microscopic studies were performed. Thirty min occlusion induced mitochondrial dysfunction without leakage of lysosomal enzymes. Reperfusion for 1 h reversed these changes. However occlusion for 2 h induced mitochondrial dysfunction associated with the leakage of lysosomal enzymes, and mitochondrial dysfunction was not reversed by 1 h reperfusion. Propranolol reduced mitochondrial dysfunction after 2 h occlusion and prevented leakage of lysosomal enzymes. Mitochondrial function was fairly well maintained after 1 h reperfusion in dogs premedicated with propranolol. Structural changes in mitochondria were observed in the 2 h occlusion/l h reperfusion group, and were reduced by premedication with propranolol. These results suggest that irreversible injury of ischaemic mitochondria is closely linked with instability of lysosomal membranes, and that propranolol prevented irreversible myocardial mitochondrial dysfunction.
Cardiovasc Res 1989 May
PMID:Biochemical and morphological changes in myocardium during coronary occlusion and reperfusion in canine hearts: effects of propranolol on myocardial damage. 261 9

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)
Cardiovasc Res 1988 Mar
PMID:Prostaglandin I2 analogue and propranolol prevent ischaemia induced mitochondrial dysfunction through the stabilisation of lysosomal membranes. 304 92

Degenerative dysfunction of cardiac valves may be accounted for by uncontrolled extracellular matrix degradation processes in which matrix metalloproteinases could play a major role. In this study, 24 pathologic human valves and 26 pericardial-derived bioprostheses were analysed for metalloproteinases by gelatin zymography. Compared to controls, human stenotic valves and bioprostheses explanted because of either calcifying or noncalcifying degeneration revealed three notable biochemical aspects: (1) an amplification in the levels of metalloproteinase 9 (gelatinase B), suggestive of its active role in valvular pathology; (2) minimal modifications in the gelatinolytic levels of metalloproteinase 2 (gelatinase A), indicative of a constitutive secretion; and (3) activation products derived from both gelatinase A and B. All gelatinolytic activities identified in pathologic specimens were inhibited in vitro by zinc and calcium chelators (captopril, doxycycline, dithiothreitol, and ethylenediaminotetraacetic acid), suggesting potential therapeutic approaches. High levels of beta-glucuronidase (a lysosomal marker enzyme for phagocytic cells) were found in human calcified stenotic valves and in ruptured and calcified pericardial-derived bioprostheses. Mononuclear recruitment was minimal to moderate in pathologic human valves, and in noncalcified ruptured bioprostheses infiltrating mononuclear cells were concentrated in large numbers at the cuspal free edge. These findings suggest the involvement of infiltrating phagocytic cells and putative common mechanisms in the degeneration of both the natural and the bioprosthetic valvular extracellular matrix (ECM).
Cardiovasc Pathol
PMID:Matrix metalloproteinases in the pathology of natural and bioprosthetic cardiac valves. 2585 89