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

In order to evaluate the possible role of the hepatic macrophage (H-M macrophage) in lipopolysaccharide-induced shock and disseminated intravascular coagulation (DIC), a technique has been developed for the isolation and maintenance in culture of rabbit H-M macrophage. Characterization of the resultant cell population by morphology, nonspecific esterase staining, phagocytosis of latex beads, by presence of Fc and C3b membrane receptors confirms a pure population of M macrophage without outgrowth of other cell types for up to 10 days in culture. The exposure in vitro of the H-M macrophage to LPS (either Salmonella minnesota R595 or Escherichia coli 0111:B4) stimulates a selective increase in activity of several cellular enzyme: LDH, lysozyme, plasminogen activator, and a procoagulant factor, with minimal changes in acid phosphatase and beta-glucuronidase detected. Concomitantly, both in vivo and in vitro treatment with LPS produces an apparent direct cellular toxicity. The combined effect of toxicity and selective stimulation and release of mediators in LPS-stimulated H-M macrophage may play a central role in the endotoxemic shock syndrome.
 ...
PMID:The response of isolated rabbit hepatic macrophages (H-M macrophage) to lipopolysaccharide (LPS). 719 47

The effect of bacterial endotoxin (LPS) on lysosomal enzyme activities of fibroblasts from normals and mucolipidosis III patients was investigated. Exposure of normal fibroblasts to LPS for 24 hours resulted in enhanced intracellular activities of beta-glucuronidase, beta-galactosidase, alpha-L-iduronidase and beta-N-acetylglucosaminidase. Endotoxin also led to an increased extracellular activity of beta-N-acetylglucosaminidase. In contrast, mucolipidosis III fibroblasts did not show either intracellular or extracellular increase of lysosomal hydrolases after LPS treatment. Difference in cellular responsiveness to LPS may be related to the mechanism of LPS-cell interaction.
 ...
PMID:Effect of bacterial endotoxin on lysosomal enzyme activities of normal and mucolipidosis III fibroblasts. 726 Feb 37

CD14 is a glycosylphosphatidylinositol (GPI)-anchored protein on the surfaces of monocytes and polymorphonuclear leukocytes (PMN) that binds and initiates cellular responses to bacterial LPS. PMN also contain an intracellular pool of CD14 that can be deployed rapidly to the cell surface in response to stimulation with a variety of agonists. To determine which of the well-characterized subcellular compartments of PMN contains CD14, cells were cavitated and fractionated on Percoll gradients. The gradient fractions were assayed for CD14 by ELISA and Western blot and for the marker proteins beta-glucuronidase (azurophil granules), vitamin B12 binding protein (specific granules), alkaline phosphatase (secretory vesicles and plasma membrane), and HLA (plasma membrane). Approximately one-half of the CD14 ran with plasma membrane fractions and one-half with intracellular membranes of light density. Both intracellular and cell surface CD14 were associated tightly with membrane, and both forms showed identical electrophoretic mobility. The intracellular CD14 was clearly not present in azurophil granules or specific granules, but ran precisely with alkaline phosphatase, a marker for secretory vesicles. Parallel studies showed that an additional GPI-linked protein, Fc gamma RIII (CD16), also fractionated precisely with CD14 and alkaline phosphatase. Association of CD14 with secretory vesicles were confirmed by studies on cells stimulated with the formyl peptide fNLLP for 20 min at 37 degrees C before fractionation. This treatment caused translocation of CD14 from intracellular fractions to plasma membrane fractions. No release of the specific granule marker vitamin B12 binding protein was observed under these conditions, whereas two other GPI-anchored proteins, alkaline phosphatase and CD16, moved coincidentally with CD14 to comigrate with the plasma membrane. Time course studies of CD14 and CD16 surface expression confirmed the rapid and coordinate up-regulation of these proteins. Thus, the intracellular compartment containing CD14 and CD16 had the properties of secretory vesicles. These vesicles may represent a specialized membrane domain of PMN enriched in GPI-anchored proteins.
 ...
PMID:Endotoxin receptors (CD14) are found with CD16 (Fc gamma RIII) in an intracellular compartment of neutrophils that contains alkaline phosphatase. 754 38

We found a new, highly selective plasma kallikrein inhibitor, trans-4-aminomethyl-cyclohexanecarbonylphenylalanine 4-carboxymethylanilide hydrochloride, called PKSI-527 in our laboratories. This study was conducted to evaluate PKSI-527, on thromboplastin (TP)- and endotoxin (LPS)-induced disseminated intravascular coagulation (DIC) in rats. PKSI-527 was infused intravenously at 0.1 mg/kg/min for 250 min. Three of the parameters of the coagulation and fibrinolysis system, fibrinogen level, platelet counts and fibrin(ogen) degradation products (FDP) level were assayed. PKSI-527 prevented the change in the coagulation and fibrinolysis system in LPS-induced DIC, however it was not clearly effective in TP-induced DIC. The parameters of organ failure, such as serum glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), creatine phosphokinase (CPK), lactate, blood urea nitrogen and beta-glucuronidase, were assayed. Although the changes in the fibrinogen level, platelet counts and FDP level were almost the same in both models, the parameters of organ failure apparently increased in LPS-induced DIC more so than in TP-induced DIC. PKSI-527 significantly suppressed the increases in GOT and GPT in LPS-induced DIC. These results indicate that plasma kallikrein may play a significant role in LPS-induced DIC. Therefore, PKSI-527, as a synthetic plasma kallikrein inhibitor may be a valuable tool to explore the mechanism of DIC and the accompanying organ failure.
 ...
PMID:Effects of a highly selective synthetic inhibitor of plasma kallikrein on disseminated intravascular coagulation in rats. 874 31

We previously reported that both local and systemic factors relevant to the pathogenesis of periodontal disease can increase gingival collagenase activity in rats. Since the degradation of extracellular matrix is an essential feature of periodontal disease and this tissue breakdown requires multiple enzyme interactions, the current study was carried out to determine the effects of bacterial endotoxin (LPS) (a local factor) and diabetes (a systemic factor) on a panel of matrix-degrading enzymes (collagenase, gelatinase, elastase, and beta-glucuronidase) in the gingiva of rats. In addition, the effects of therapy with a semisynthetic tetracycline (minocycline) were investigated. Ten male, Sprague-Dawley rats were made diabetic by IV injection of streptozotocin. Four of the ten rats then received minocycline (10 mg/day) by oral gavage on a daily basis for 3 weeks. Nineteen nondiabetic rats served as controls and 9 of them received 10 microliters of E. coli LPS (10 mg/ml) by injection into the labial gingiva every other day during the last week of the study. The other 10 nondiabetic rats were sham injected with saline into the gingiva. At the end of the 3 week experimental period, gingival tissue and skin were dissected from each rat and extracted for enzyme analysis. Our results showed that diabetes markedly increased the four matrix-degrading enzyme activities in both gingiva and skin. In contrast, local LPS injection increased these enzyme activities in the gingiva alone. Systemic therapy with minocycline completely ameliorated these elevated enzyme levels in diabetic rats in both gingiva and skin. Minocycline added in vitro to the enzyme assay systems containing skin extract from diabetic rats also inhibited collagenase and gelatinase activities, but no inhibition was observed for elastase and beta-glucuronidase activities, indicating that the MMPs and other enzymes were inhibited by minocycline, during diabetes, by indirect and indirect mechanisms, respectively.
 ...
PMID:Local and systemic factors in periodontal disease increase matrix-degrading enzyme activities in rat gingiva: effect of micocycline therapy. 882 70

Sphingosine kinase (SPHK) has been implicated as an important element in neutrophil responses to diverse stimulatory agents. To get more insight into the role of the type 1 and 2 isoforms of SPHK in neutrophil functions, we made use of the respective SPHK knockout mice. Neutrophils isolated from the bone marrow of these mice showed normal increase of intracellular Ca(2+) when stimulated in vitro by fMLP, platelet-activating factor, the anaphylatoxin C5a, or ATP, and normal migration towards fMLP and C5a. Also, recruitment of neutrophils into the peritoneum towards the chemokines KC and MIP-2 or to LPS, and into the peripheral blood after fMLP injection was similar in SPHK knockout strains and wild-type animals. An in vivo model of bacterial lung infection revealed an accelerated progression of disease in SPHK2 (but not SPHK1) knockout mice as compared to wild-type controls. However, effector functions of SPHK-deficient neutrophils, such as superoxide production, beta-glucuronidase release and their capacity to kill bacteria were unchanged as compared to wild-type cells. To conclude, the data derived from SPHK knockout mice do not support the hypothesis that any of the two lipid kinases plays a crucial role in signalling downstream of various neutrophil stimuli; SPHKs appear not to be essential for neutrophil recruitment and effector functions.
 ...
PMID:Normal neutrophil functions in sphingosine kinase type 1 and 2 knockout mice. 1729 73

Mitochondria and lysosomes were evaluated by assessment of changes in activity of selected enzymes: lactate dehydrogenase (LDH), succinate dehydrogenase (SDH), adenosinetriphosphatase (ATPase), acid phosphatase (AcPase) and beta-glucuronidase (BG) in rats under profound hypoxia induced by endotoxemic shock. The study was conducted on adult male Wistar rats. The animals formed the following four groups of 15 rats each: control animals (C);-rats receiving intraperitonally O(2)/O(3) (CO), rats receiving of Escherichia coli toxin (LPS) (CL); rats receiving LPS plus oxygen-ozone mixture (OL). Histoenzymatic examinations of liver, kidney, lungs, and heart muscle were performed. Lipopolysaccharide suppressed activities of all the enzymes except for LDH, the activity of which as high as a fourfold increase. The results demonstrated potent, stabilizing and regenerative effects of ozone therapy on body enzymatic processes in course of induced endotoxemic shock in rats, which might prove to be of clinical significance.
 ...
PMID:Ozone therapy in induced endotoxemic shock. II. The effect of ozone therapy upon selected histochemical reactions in organs of rats in endotoxemic shock. 1745 89

Synthesis and anti-inflammatory effects of certain furo[3',2':3,4]naphtho[1,2-d]imidazole derivatives 12-18 were studied. These compounds were synthesized from naphtho[1,2-b]furan-4,5-dione (10) which in turn was prepared from the known 2-hydroxy-1,4-naphthoquinone (7) in a one pot reaction. Furo[3',2':3,4]naphtho[1,2-d]imidazole (12) was inactive (IC(50) value of >30 microM) while its 5-phenyl derivative 13, with an IC(50) value of 16.3 and 11.4 microM against lysozyme and beta-glucuronidase release, respectively, was comparable to the positive trifluoperazine. The same potency was observed for 5-furan derivative 16 with an IC(50) value of 19.5 and 11.3 microM against lysozyme and beta-glucuronidase release, respectively. An electron-withdrawing NO(2) substituted on 5-phenyl or 5-furanyl group led to the devoid of activity as in the cases of 14 and 17. Among them, compound 15 exhibited significant inhibitory effects, with an IC(50) value of 7.4 and 5.0 microM against lysozyme and beta-glucuronidase release, respectively. For the LPS-induced NO production, the phenyl derivatives 12-15 were inactive while the nitrofuran counterparts 17 and 18 suppress LPS-induced NO production significantly, with an IC(50) value of 1.5 and 1.3 microM, respectively, which are more active than that of the positive 1400 W. Compounds 16-18 were capable of inhibiting LPS-induced iNOS protein expression at a dose-dependent manner in which compound 18, with an IC(50) of 0.52 microM in the inhibition of iNOS expression, is approximately fivefold more potent than that of the positive 1400 W. In the CLP rat animal model, compound 18 was found to be more active than the positive hydrocortisone in the inhibition of the iNOS mRNA expression in rat lung tissue. The sepsis-induced PGE2 production in rat serum decreased 150% by the pretreatment of 18 in a dose of 10 mg/kg.
 ...
PMID:Furo[3',2':3,4]naphtho[1,2-d]imidazole derivatives as potential inhibitors of inflammatory factors in sepsis. 1969 97