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)

Platelets contain a polypeptide growth factor that stimulates the replication of normal connective tissue cells; this platelet-derived growth factor (PDGF) is released during the clotting process. Human platelets from normal volunteers were disrupted by nitrogen cavitation, and the subcellular organelles were fractionated by ultracentrifugation through a 30%--60% sucrose gradient. Electron microscopy revealed that fraction 7 (density 1.23 g/liter) contained the largest number of alpha granules. The specific activity of platelet fibrinogen, an alpha-granule marker, was also highest in this fraction. The subcellular fractions were assay for the presence of PDGF and for beta-thromboglobulin. PDGF was assayed quantitatively by the stimulation of DNA synthesis in confluent growth-arrested BALB/c-3T3 cells, whereas the concentration of beta-thromboglobulin was determined by radioimmunoassay. The highest concentrations of both PDGF and beta-thromboglobulin were found in the alpha-granule fraction. In contrast, beta-glucuronidase, a lysosomal enzyme, was more diffusely distributed and had its highest specific activity in fractions of lower density than those for PDGS, beta-thromboglobulin, or fibrinogen. The data demonstrate that the alpha granules of platelets provide a unique delivery system for PDGF, a polypeptide hormone with growth-promoting activity for connective tissue cells.
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PMID:Platelet alpha granules contain a growth factor for fibroblasts. 44 48

We showed by immunofluorescence, immunoelectron microscopy and Western blot analysis that the plasma glycoprotein (gp60), an Fc gamma binding protein which inhibits complement-mediated prevention of immune precipitation, is present in platelets. The gp60 content of platelets in normal individuals and patients with rheumatoid arthritis was similar (mean 0.028 and 0.024 fg/platelet respectively). Immunoelectron microscopic studies showed that gp60 was present in the cytoplasm and the surface connecting structures but not in the alpha granules, dense granules or lysosomes. Using this technique gp60 was also found on platelet membranes, an observation which was confirmed by immunofluorescence. Activation of platelets with thrombin, calcium ionophore, and immune complexes (IC) resulted in the release of the contents of the alpha granules (beta-thromboglobulin), dense granules (5-hydroxytryptamine) and lysosomes (beta-glucuronidase) but did not induce gp60 secretion. The inability of Fab anti-gp60 to inhibit IC-mediated platelet aggregation and of F(ab')2 anti-gp60 to produce platelet aggregation suggested that IC-mediated platelet aggregation did not occur as a result of the interaction of IC with platelet gp60. However, as the preincubation of IC with purified gp60 produced dose-dependent inhibition of the ability of IC to aggregate platelets it is possible that fluid-phase plasma gp60 modulates the interaction of IC with platelets.
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PMID:Immunohistochemical and functional studies of glycoprotein 60 (gp60) in platelets. 157 4

Purification of monocyte-derived NAP-1/IL-8 by preparative reversed-phase (RP)-HPLC led to the detection of a second peak with polymorphonuclear leukocyte (PMNL)-activating (degranulation, chemotaxis) properties. The monokine responsible for this biological activity, which we tentatively termed NAP-3, could be purified to homogeneity by three different RP-HPLC steps. Tricine-SDS-PAGE analysis gave a single line at Mr 5.3 kD (NAP-1/IL-8 = 5.8 kD). NH2-terminal amino acid sequence analysis read as a major sequence (ASVATELRXCXLQT. .), which shows greater than 40% homology to that of NAP-1/IL-8. The sequence is identical to that found for the 13-kD moiety of melanoma growth stimulating activity (MGSA) and the product of the oncogene gro. Determination of neutrophil chemotactic activity of NAP-3 revealed a typical bell-shaped dose-response curve (ED50 = 2 ng/ml) with no significant neutrophil chemotactic activity at doses greater than 200 ng/ml. Also, in cytochalasin B-pretreated PMNL, NAP-3 elicited release of myeloperoxidase and beta-glucuronidase. Crossdesensitization studies in PMNL enzyme release revealed crossreactivities with the NAP-1/IL-8-R on PMNL. NAP-3 (MGSA/gro) appears to represent the first member of the novel supergene family of beta-thromboglobulin-like host defense cytokines, which expresses both mitogenic as well as proinflammatory properties at the nanogram level.
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PMID:Lipopolysaccharide-stimulated human monocytes secrete, apart from neutrophil-activating peptide 1/interleukin 8, a second neutrophil-activating protein. NH2-terminal amino acid sequence identity with melanoma growth stimulatory activity. 218 61

The cytochemical features of blast cells were studied in 45 patients with blastic phase of chronic granulocytic leukaemia. Various degrees of Sudan black B positivity was characteristic of myeloblastic transformation (23 patients), while in the medullary blast cells of nine patients with myelomonocytic transformation the alpha-naphthyl-acetate esterase showed intensive activity. In two cases the demonstrability of beta-thromboglobulin and factor VIII-related antigen in blast cells showing otherwise PAS, acid phosphatase and alpha-naphthyl-acetate esterase activity referred to megakaryocytic transformation. In six patients with lymphoid blast crisis proliferation of the Sudan negative blast cells with different granular PAS, acid phosphatase and/or beta-glucuronidase positivity was demonstrated. In five cases the cytochemical findings of leukaemic cells indicated biphenotypic and mixed transformation, respectively.
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PMID:Cytochemical studies in the blastic transformation of chronic granulocytic leukaemia. 247 28

Platelets contain mitogenic activities for MCF-7 human breast cancer cells when assayed under serum-free chemically defined conditions. Purification from outdated human platelets identified insulinlike growth factor I (IGF-I) as the most potent breast cancer cell mitogen in lysates (Karey KP, Sirbasku DA: see accompanying article, this issue). In this study the release and subcellular localization of IGF-I was investigated. Degranulation of platelets by thrombin treatment caused release of lysosomal enzymes (beta-glucuronidase and N-acetyl-D-glucosaminidase), alpha-granule proteins (beta-thromboglobulin and fibrinogen) as well as mitogenic activity for MCF-7 cells and IGF-I as measured by radioimmunoassay (RIA) and radioreceptor assay. Release of mitogenic activity and immunologically identified IGF-I was induced tenfold over controls by thrombin and was nearly complete as compared to platelets disrupted by repeated freezing and thawing. Disruption of platelets by nitrogen cavitation followed by separation of the organelles by sucrose density gradient sedimentation showed that IGF-I and mitogenic activity localized predominantly to fractions containing alpha-granules rather than soluble cellular components, lysosomes, or dense granules. The morphology of MCF-7 cells in serum-free medium supplemented with supernatants from thrombin-treated platelets also indicated the release of important cell-adhesion factors for human breast cancer cells.
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PMID:Human platelet-derived mitogens. II. Subcellular localization of insulinlike growth factor I to the alpha-granule and release in response to thrombin. 275 54

Structurally intact platelet cohorts of differing densities can be isolated from normal subjects by the use of isosmolar arabinogalactan density gradients. Using platelets separated in this fashion, we have studied the density-dependent distribution of four subcellular organelles: mitochondria, lysosomes, dense bodies, and alpha granules. Mitochondria, which are not secreted during platelet release, demonstrate a slow decline in monoamine oxidase activity within the gradient. Lysosomal beta-glucuronidase does not vary significantly with platelet density. In contrast, dense body number and endogenous serotonin content decrease significantly with decreasing platelet density, primarily as the result of differences in the number of storage organelles. Platelet factor 4 content declines rapidly in comparison to lysosomal activities (P less than .001 from bottom to top of the gradient); but beta-thromboglobulin, also an alpha granule component, exhibits considerably less change than platelet factor 4 (P less than .001). Thus, specific platelet subcellular constituents have different density distributions. We postulate that these density differences may be due to differential in vivo loss of selective biochemical constituents from unique subcellular compartments.
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PMID:Heterogeneity of human whole blood platelet subpopulations. III. Density-dependent differences in subcellular constituents. 623 35

Acquired abnormalities of platelet aggregation have been reported with increasing frequency. We studied five patients (including two with systemic lupus erythematosus and one with compensated chronic idiopathic thrombocytopenic purpura) in whom platelet aggregation responses to collagen, epinephrine and ADP are impaired; in all cases, we found that levels of platelet-associated immunoglobulin G (IgG) were increased. In all five patients substances stored in platelet-dense granules (ATP, ADP, serotonin and calcium) were diminished. The content of the alpha-granule substance, beta-thromboglobulin, was also decreased in most cases, whereas the levels of two secretable acid hydrolase enzymes (beta-glucuronidase and beta-N-acetyl glucosaminidase) were within normal limits. These findings are similar to those observed in subtypes of congenital storage pool deficiency. However, in contrast to the congenital disorder, a membrane-bound (nonsecretable) acid phosphatase was also decreased in the patients with acquired storage pool deficiency. These findings suggest that impaired platelet aggregation on an acquired basis may, in some patients, be due to immune platelet damage resulting in a distinctive type of platelet storage pool deficiency.
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PMID:Acquired storage pool deficiency with increased platelet-associated IgG. Report of five cases. 644 50

We have studied the regeneration of adenosine triphosphate (ATP) in the glycolytic pathway in platelets with a 75% reduction in hexokinase (HK) activity and have investigated aggregation and Ca2+ secretion. HK-deficient platelets had a normal glycolytic flux in the resting state, but responded insufficiently to stimulation with thrombin (5 U/ml). In contrast, glycogen contents and glycogenolysis were normal. When the metabolic adenine nucleotides were labeled with 14C-adenine, the patient's platelets showed a normal adenylate energy charge and a normal level of 14C-ATP. However, the inhibitor of mitochondrial energy generation, CN-, induced a weaker fall in 14C-ATP in the patient's platelets than in the controls. Analysis of secretion markers revealed decreased amounts of granule-bound ATP and secretable Ca2+, whereas granule-bound adenosine diphosphate (ADP), beta-thromboglobulin, N-acetyl-beta-D-glucosaminidase, and beta-glucuronidase were within the normal range. Aggregation and Ca2+ secretion induced by 5 U/ml thrombin were normal and were not changed in the presence of inhibitors of mitochondrial and glycogenolytic energy generation. Aggregation was also normal at 0.1 U/ml thrombin and was independent of these inhibitors, but Ca2+ secretion was greatly impaired when mitochondrial and glycogenolytic ATP resynthesis was abolished. These findings indicate that a severe reduction in HK activity causes insufficient acceleration of the glycolytic flux during stimulation with thrombin. This leads to impaired dense granule secretion in conditions where secretion depends on concurrent ATP resynthesis and glycolysis is rate limiting.
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PMID:Platelet functions and energy metabolism in a patient with hexokinase deficiency. 668 46

The contact of blood with the artificial extracorporeal circuit causes a systemic inflammatory response due to blood activation. In this study, we compared two different paediatric membrane oxygenators used for extracorporeal circulation: a hollow fibre membrane oxygenator (Dideco Masterflo D-701, n = 10), and a flat sheet silicone membrane oxygenator (Avecor Kolobow 800-2A, n = 10). Blood compatibility was indicated by measuring complement activation as well as leukocyte and platelet activation. In patients perfused with a flat sheet membrane oxygenator, concentrations of complement split products C3a were significantly increased 30 minutes after the start of bypass (p < 0.01), whereas only a mild increase of C3a was found in patients perfused with a hollow fibre membrane oxygenator. Leukocyte and platelet counts dropped uniformly in both groups after the start of bypass mainly due to hemodilution. Activation of leukocytes and platelets identified by both plasma beta-glucuronidase and beta-thromboglobulin was similar in both groups. Infants perfused with a flat sheet membrane oxygenator received significantly more donor blood than those perfused with a hollow fibre oxygenator (p < 0.05). These results indicate that when used during paediatric cardiopulmonary bypass, a flat sheet membrane oxygenator has a higher complement activity than a hollow fibre membrane oxygenator, which is probably due to the relatively larger blood-surface contacting area of the oxygenator.
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PMID:Blood compatibility of two different types of membrane oxygenator during cardiopulmonary bypass in infants. 789 28

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