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

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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.
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PMID:Protective effect of methylprednisolone on the heart during ischemic arrest. 17 23

Myocardial ischemia was produced for 2 hours by coronary ligation in 11 dogs pretreated with methylprednisolone (MP, 30 mg/kg). Myocardial blood flow (MBF) was measured with microspheres (15 micrometer) in each tissue sample used for enzymatic analysis. Homogenates of these tissue samples were separated by ultracentrifugation into lysosome-rich and microsomal fractions and were analyzed for N-acetyl-beta-glusosaminidase (NAGA), beta-glucuronidase (beta-gluc), rotenone-insensitive-NADH-cytochrome c reductase (RINCR), and cytochrome oxidase. The enzymatic data from centrifugal fractions were grouped according to MBF values for statistical analysis of inter-group effects of ischemia. Significant losses (P less than 0.001) of NAGA and beta-gluc were seen in all MP-treated lysosome-rich particulate fractions that were isolated from zones demonstrating MBF values less than 25% of control (L-ischemia). Similar significant losses (P less than 0.001) of RINCR were seen in microsomal fractions from L-ischemia zones. Samples with MBF values greater than 25% but less than 75% of control (M-ischemia) also demonstrated significant decreases of lysosomal and microsomal enzymatic activity in specific fractions. When the data of the above MP-treated group were compared with the untreated control group, no significant intergroup effects of treatment with MP were observed. In addition, enzymatic data (NAGA, RINCR) were normalized prior to performing linear regression analyses; percent loss of particulate enzymatic activity was plotted against percent decrease in MBF. The effects of 2 hours of ischemia on the above biochemical parameters were comparable between untreated and MP-treated groups. Finally, when myocardial samples were grouped according to similar levels of MBF, statistical analysis using the general linear models procedure revealed no beneficial effect of MP treatment on changes in lysosomal hydrolases, microsomal RINCR, or latency of lysosomes.
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PMID:Lack of effect of methylprednisolone on lysosomal and microsomal enzymes after two hours of well-defined canine myocardial ischemia. 21 3

Twenty-two cat hearts were perfused according to Langendorff technique and myocardial regional ischemia was induced by occlusion of left anterior coronary artery. Separation of particulate (bound) from soluble (free) fraction, and subsequent fractionation into plasma membranes, lysosomes, sarcoplasmic reticulum, and mitochondria were performed by sucrose density gradient ultracentrifugation. By ischemia for 60 min, particle-bound activity of cathepsin D decreased from 4.2 +/- 0.24 U/mg protein to 3.2 +/- 0.31 U/mg protein (p less than 0.01). Likewise, the particle-bound activity of beta-glucuronidase decreased from 11.9 +/- 0.92 U/mg protein to 6.2 +/- 1.28 U/mg protein (p less than 0.01). Accordingly, free/bound activity ratios of cathepsin D increased from 0.8 to 1.9 and beta-glucuronidase from 0.9 to 2.8, respectively. Conspicuous fall from 12.8 +/- 0.6 U/mg protein to 8.0 +/- 0.97 U/mg protein (p less than 0.01) in absolute specific activity of cathepsin D bound to the lysosomal fraction, presents definitive evidence of lysosomal release of the acid hydrolases during the early phase of myocardial ischemia. Electron microscopic observation of the ischemic myocytes revealed ultrastructural alterations of the lysosomes suggestive of autophagic degradation of various subcellular organelles.
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PMID:Lysosomal hypothesis in evolution of myocardial infarction. Subcellular fractionation and electron microscopic cytochemical study. 50 30

The pathobiology of the process of myocardial injury during ischemia comprises a series of events that results in the release of lysosomal enzymes from their subcellular locations within the myocardium. We have developed a canine model of acute myocardial ischemia in which the anterior descending coronary artery is ligated, myocardial blood flow is measured using radioactive microspheres, and tissues from subendocardium and subepicardium are assayed for activity of lysosomal hydrolases:N-acetyl-beta-glucosaminidase (NAG), beta-glucuronidase (beta-gluc), and acid phosphatase (AP). Particulate fractions of subendocardium revealed significant depletion of of total acid hydrolases (NAG, beta-gluc, and AP) after one and two hours of ischemia. In addition, after two hours of ischemia, the total activity of these three hydrolases in the subendocardial supernatant was decreased, correlating significantly with diminished myocardial blood flow (NAG: r =0.96; beta-gluc: r = 0.95; AP: r = 0.75). The diminished enzymatic levels in thesupernatant suggested "washout" of the hydrolases that was more efficient in those ischemic areas that had higher myocardial flow (greater than 20% of control). These changes in distribution of lysosomal hydrolases indicate early involvement of these enzymes in the pathobiology of myocardial injury and demonstrate the dynamic relationship of "washout" of acid hydrolases with the degree of diminished blood flow.
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PMID:Release of lysosomal enzymes during ischemic injury of canine myocardium. 103 97

In ischemia-reflow states of coronary artery disease, the activation of PMN precedes the initiation of tissue damage. Release of atrial natriuretic peptide (ANP) from myocytes occurs within minutes after the onset of myocardial ischemia, which suggests a possible role of ANP in PMN activation. To investigate this possibility, we tested the effects of ANP on functions of PMN in vitro. ANP is a potent signal for priming the PMN respiration burst to secrete superoxide anion. Phorbol 12-myristate 13-acetate, opsonized zymosan, or FMLP could all be used as triggering stimuli to demonstrate the priming of PMN activation by ANP. Only ANP fragments 1-28 and 7-28 enhanced respiration burst activity but identical preparations of ANP fragments 13-18 or 1-11 failed to do so. This structure-activity relationship is typical of receptors for ANP found in other tissues. In addition, ANP stimulated the release of beta-glucuronidase From PMN triggered by FMLP. The observed inhibition by ANP of FMLP-stimulated chemotaxis of PMN may be due to their enhanced adhesiveness. These data show that a classic cardiac hormone is involved in regulating important functional activities of PMN. These data support the possibility that ANP could act as a preinflammatory substance in ischemia-reperfusion states and myocardial necrosis.
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PMID:Priming of polymorphonuclear neutrophils by atrial natriuretic peptide in vitro. 131 51

Different nitrovasodilators were used to assess the role of cyclic GMP in the regulation of polymorphonuclear leukocyte (PMN) function. Molsidomine and its metabolites, 3-morpholinosydnonimine (SIN-1) and N-nitroso-N-morpholinoaminoacetonitrile (SIN-1A) at 0.01-1 mM, inhibited lysosomal enzyme release from PMN stimulated by 30 nM formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP). At 1 mM, molsidomine, SIN-1 and SIN-1A decreased beta-glucuronidase release by 19, 37 and 46% of the control, respectively. Glyceryl trinitrate (GTN) and sodium nitroprusside (SNP) showed no effect on beta-glucuronidase release from PMN. At 1 mM, SIN-1A, SIN-1 and SNP in the presence of 0.5 mM isobutylmethylxanthine (IBMX) stimulated cyclic GMP 21-, 9- and 14-fold, respectively, demonstrating a relation between cyclic GMP stimulation and neutrophil inhibition by the molsidomine metabolites. GTN and unmetabolized molsidomine were without effect on cyclic GMP levels. The hypothesis of an inhibitory effect of cyclic GMP on neutrophil function was further supported by the attenuation of SIN-1-induced inhibition of enzyme release by methylene blue (10 microM), an inhibitor of soluble guanylate cyclase. Moreover, 8-bromo cyclic GMP and dibutyryl cyclic GMP, 1 mM, decreased beta-glucuronidase release from FMLP-stimulated PMN by 12 and 44% of the control, respectively. These data demonstrate that cyclic GMP is an inhibitory second messenger in human PMN and suggest that this action of SIN-1 may be of considerable interest under conditions of platelet/PMN activation, e.g. during myocardial ischemia.
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PMID:Cyclic GMP mediates SIN-1-induced inhibition of human polymorphonuclear leukocytes. 169 5

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)
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PMID:Reduction in myocardial ischemic/reperfusion injury and neutrophil accumulation after therapeutic administration of streptokinase. 172 70

In this study, S-allyl cysteine sulfoxide (SACS) was used to evaluate its preventive effect in isoproterenol (ISO)-induced myocardial ischemia in male Wistar rats. Rats were pretreated with SACS (40 and 80 mg kg(-1)) orally for 5 weeks. After the treatment period, ISO (150 mg kg(-1)) was administered subcutaneously to rats at an interval of 24 h for 2 days. The activities of beta-D-N-acetyl-glucosaminidase, beta-galactosidase, beta-glucosidase, and acid phosphatase increased in serum and heart in ISO-induced rats. In addition, these rats showed a significant (p < 0.05) increase in the activities of beta-glucuronidase and cathepsin-D in serum and heart and a significant (p < 0.05) decrease in their activities in lysosomal fraction of the heart. The activity of Na(+)K(+)-ATPase declined, while those of Ca(2+)- and Mg(2+)-ATPases significantly (p < 0.05) elevated in the heart of ISO-induced rats. Pretreatment with SACS (40 and 80 mg kg(-1)) showed a significant (p < 0.05) effect in all the biochemical parameters studied. The effect at a dose of 80 mg kg(-1) body weight was more effective than that at 40 mg kg(-1) body weight and brought back all the biochemical parameters to near normal levels. Hereby, our study shows the membrane-stabilizing as well as antioxidant effects of SACS in ISO-induced rats.
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PMID:Preventive effect of S-allyl cysteine sulfoxide (alliin) on lysosomal hydrolases and membrane-bound ATPases in isoproterenol-induced myocardial infarction in Wistar rats. 1762 87

The aim of this study was to evaluate the time course events of cellular damage during myocardial ischemia and reperfusion injury in rats and to find out a correlation between the structural alterations with respect to the biochemical changes. Cardiac biomarkers and lysosomal enzymes viz. cathepsin D, acid phosphatase and beta-glucuronidase and matrix metalloproteinases (MMPs) were evaluated at different time points, in response to ischemia-reperfusion induced oxidative stress in an isolated rat heart model perfused in Langendorff mode. Microscopically, changes in myocardial architecture, myofibrillar degradation, and collagen (COL) integrity were studied using hematoxylin-eosin, Masson's trichrome and toluidine blue staining techniques. A three-fold increase in the level of myoglobin was observed after 30 min of ischemia followed by 120 min of reperfusion as compared to 15 min ischemia, 120 min reperfusion. Similarly, a significant increase (P<0.05) in the levels of lipid peroxides and superoxide anion coupled with a decrease in enzymatic and nonenzymatic antioxidant levels were observed. A concomitant increase in the activity of cathepsin D (24.07+/-0.95) and a higher expression of MMPs after 120 min of reperfusion following 30 min ischemia were shown to correlate with the myocardial damage as shown by histopathology, suggesting that free radical induced activation of cathepsin D and MMPs could mediate early damage during myocardial ischemia and reperfusion.
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PMID:Myocardial ischemia and reperfusion injury in rats: lysosomal hydrolases and matrix metalloproteinases mediated cellular damage. 1834 82

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