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)

C-reactive protein (CRP) is an acute phase reactant which shares numerous functional characteristics with the immunoglobulins. In the present study CRP was found to inhibit the aggregation of human platelets stimulated by either modified human immunoglobulin or thrombin. This effect did not involve chelation of calcium or cytotoxicity, and was overcome by larger amounts of the aggregating agents. CRP also inhibited the activation but not the activity of platelet factor 3 and the release of beta-glucuronidase. Thus, CRP can inhibit multiple platelet reactivities. We suggest that this property of CRP may play an important role in the control of platelet responsiveness during reactions of inflammation, defense, and repair.
 ...
PMID:Effects of C-reactive protein on platelet function. I. Inhibition of platelet aggregation and release reactions. 5 27

Ca2+, Mg2+-ionophores X537A and A23,187 (10(-7)-10(-6) M) induced the release of adenine nucleotides adenosine diphosphate (ADP, adenosine triphosphate (ATP), serotonin, beta-glucuronidase, Ca2+, and Mg2+ from washed human platelets. Enzymes present in the cytoplasm or mitochondria, and Zn2+ were not released. The rate of ATP and Ca2+ release measured by firefly lantern extract and murexide dye, respectively, was equivalent to that produced by the physiological stimulant thrombin. Ionophore-induced release of ADP, and serotonin was substantially (approximately 60%) but not completely inhibited by EGTA, EDTA, and high extracellular Mg2+, without significant reduction of Ca2+ release. The ionophore-induced release reaction is therefore partly dependent upon uptake of extracellular Ca2+ (demonstrated using 45Ca), but also occurs to a significant extent due to release into the cytoplasm of intracellular Ca2+. The ionophore-induced release reaction and aggregation of platelets could be blocked by prostaglandin E1 (PGE1) or dibutyryl cyclic AMP. The effects of PGE1, and N6, O2-dibutyryl adenosine 3':5'-cyclic monophosphoric acid (dibutyryl cAMP) were synergistically potentiated by the phosphodiesterase inhibitor theophylline. It is proposed that Ca2+ is the physiological trigger for platelet secretion and aggregation and that its intracellular effects are strongly modulated by adenosine 3':5'-cyclic monophosphoric acid (cyclic AMP).
 ...
PMID:Human platelet secretion and aggregation induced by calcium ionophores. Inhibition by PGE1 and dibutyryl cyclic AMP. 17 96

The effects of DMSO are thought to result from the formation of hydrogen bonds with proton-donor groups on biopolymers, which are stronger than those formed with water. Since DMSO contains methyl groups, however, effects on hydrophobic bonding in proteins could be expected at higher DMSO levels. Our studies of the effects of DMSO on model subunit proteins can be interpreted in the above terms. At a concentration of 20% or less, DMSO changed glutamate dehydrogenase into the inactive monomer and the effects were fully reversible with the activator (ADP). Higher DMSO levels resulted in irreversible inactivation. The predominant effect noted on beta-glucuronidase was irreversible inactivation by 20% or more DMSO at 37 degrees C. Purified beta-glucuronidase exhibited an activation in 20% DMSO at high substrate levels; this resulted from an apparent substrate inhibition in the absence of DMSO. DMSO inhibited the clotting of fibrinogen by purified thrombin, but the major effect appeared to be due to competition between thrombin and DMSO for binding sites on fibrinogen. These effects appear to be largely due to interactions between DMSO and hydrophobic bonding in fibrinogen, although DMSO also appears to interfere with the aggregation of fibrin monomers through its effects on hydrophilic groups. These results suggest that reversible alterations in protein structure are the major effect of exposure of subunit proteins to low DMSO levels at low temperatues, while irreversible denaturation of subunit proteins may be an appreciable effect a higher temperatures and higher DMSO concentrations.
 ...
PMID:Effects of dimethyl sulfoxide on subunit proteins. 23 13

In 12 dogs with acute experimental pancreatitis (AEP) and 6 control animals the "free", "latent" and "total" activity of acid phosphatase, beta-glucuronidase and cathepsins in whole homogenates of the pancreas, in a lysosomal-enriched subfraction and the supernatant of pancreatic tissue was estimated. AEP was induced by injection of bile salts and thrombin solution into the pancreatic duct. In 6 dogs the protection with heparin (1.5 mg/kg/body weight) immediately after producing AEP was applied. In AEP without any protection the free activity of hydrolases in the whole homogenate (80--90%) and in the lysosomal enriched subfraction (75--90%) was higher than in the controls (60--70% and 55--75% respectively), suggesting an augmented lysosomal fragility during the course of AEP. Heparin depressed the free activity of hydrolases to 60--80% in whole homogenates, and 64--75% in the lysosomal enriched subfraction. The release of cathepsins during incubation of the lysosomal-enriched subfraction in acidic medium was lower in the group with heparin treatment. The data obtained suggest the stabilising effect of heparin on the lysosomes of the pancreas during acute experimental pancreatitis in dogs.
 ...
PMID:The effect of heparin on lysosomes of the dog pancreas during acute experimental pancreatitis. 47 25

1. Shape change, aggregation and secretion of dense-granule constituents in platelets differ in their dependence on cellular energy metabolism. The possibility that such a difference also exists between secretion of dense-granule constituents and acid hydrolases was investigated. 2. Human platelets were incubated with [(14)C]adenine in plasma, and then washed and resuspended in salt solutions. The effects of incubating the cells with antimycin A and 2-deoxyglucose on the concentrations of [(14)C]ATP, ADP, AMP, IMP and inosine plus hypoxanthine and on thrombin-induced secretion of ATP plus ADP and acid hydrolases were studied. The metabolic inhibitors only affected (14)C-labelled nucleotides, whereas thrombin only liberated unlabelled ATP and ADP. 3. The extent of secretion decreased progressively with time during incubation with the metabolic inhibitors. At any time the secretion of acid hydrolases, beta-N-acetylglucosaminidase, beta-glucuronidase and beta-galactosidase was inhibited to a greater extent than secretion of ATP plus ADP (dense-granule secretion). 4. Incubation with the metabolic inhibitors shifted the log (dose)-response relationship to higher thrombin concentrations, and with a greater shift for acid hydrolase secretion than for dense-granule secretion. 5. Antimycin, when present alone, caused a marked decrease in the rate of acid hydrolase secretion, but had no effect on dense-granule secretion. 6. These results further support the view that acid hydrolase secretion and dense-granule secretion are separate processes with different requirements for ATP energy. Acid hydrolase secretion, but not dense-granule secretion, appears to depend on a simultaneous rapid generation of ATP, which can be accomplished by oxidative, but not by glycolytic, ATP production.
 ...
PMID:Effects of antimycin A and 2-deoxyglucose on secretion in human platelets. Differential inhibition of the secretion of acid hydrolases and adenine nucleotides. 50 92

Halofenate--free acid (HFA), the major metabolite of the hypolipidemic drug, halofenate, inhibited platelet aggregation induced by collagen and sodium arachidonate and blocked the second phase of aggregation caused by ADP, thrombin and epinephrine in human platelet-rich plasma. The aggregation of washed platelets by thrombin and collagen was also blocked. HFA also inhibited the release by thrombin and collagen of 5-hydroxytryptamine from dense granules of platelets and the release by thrombin of beta-glucuronidase from platelet alpha-granules. These inhibitory effects were concentration and time-dependent. HFA decreased platelet factor 3 activity by 31% and also inhibited the incorporation of 14C-acetate and U-14C-glucose into platelet lipids by 89% and 56% respectively. Thrombin-induced lipid peroxidation and prostaglandin formation was investigated by measuring the by-product malonyldialdehyde, and this was found to be inhibited by HFA. It is suggested that the effect of HFA on aggregation is attributable to inhibition of the release reaction which may in turn be a consequence of the effects of the drug on platelet lipid synthesis.
 ...
PMID:The effect of halofenate--free acid on aggregation--the release reaction, coagulant activity, and lipid metabolism of human platelets. 57 7

The mechanism of activation of platelets by collagen was examined. Hirudin interfered with the initial collagen-platelet interaction and both hirudin and heparin inhibited collagen-induced release of platelet granular contents. Hirudin completely inhibited the release of both [3H]5HT and beta-glucuronidase whereas heparin completely inhibited release of beta-glucuronidase but only partly inhibited release of [3H] 5HT. beta-Glucuronidase and maximal [3H] 5HT were only released when plasma was present. The results are compatible with an essential intermediary role for thrombin in collagen activation of platelets. Evidence was also obtained that von Willebrand factor may participate in this reaction.
 ...
PMID:Platelet activation in haemostasis: role of thrombin and other clotting factors in platelet-collagen interaction. 87 Mar 98

The effect of heterologous anti-human platelet antibody on human platelet function was examined in the presence and absence of whole plasma as an in vitro model for antibody-induced immune damage to cells. Heterologous IgG anti-human platelet antibody mediated platelet aggregation and released serotonin from both platelets in plasma and from platelets isolated by gel filtration and increased the availability of platelet acid phosphatase in a dose-response fashion. Anti-platelet antibody failed to release beta-glucuronidase (lysosomal enzyme marker) or cause lactic dehydrogenase loss (cytolysis). The effect of the antiplatelet antibody on platelets proceeded in the absence of complement. The active molecule in the anti-platelet antiserum was isolated in the IgG fraction and all three indicators of platelet injury were mediated by purified monomeric IgG. Thrombin was not required for the antibody-mediated effects, as three thrombin inhibitors failed to block the reaction. EDTA was an effective inhibitor, suggesting a cation requirement; however, as little as 38 muM calcium was sufficient for effective platelet aggregation and release. The inability of acetylsalicylic acid to inhibit the effect of the antiplatelet antibody suggests that heterologous antibody (IgG) induced platelet alteration proceeds by a different mechanism than that mediated by ADP and epinephrine and does not involve endogenous platelet prostaglandin synthesis.
 ...
PMID:Effect of heterologous antibody on human platelets. 94

Thrombin is known to reduce the K+ content of human platelets, but the subcellular origin of the lost K+ is not known. The effect of aggregating agents on K+ release was studied in platelets labeled in plasma by preincubation with 42KCI. Platelets were separated from plasma by gel filtration through Sepharose 2B equilibrated with K+ -free Tyrode's buffer. Platelet K+ was 116nEq/10(8) platelets, of which 23% was found to be extracellular immediately after gel filtration. K+ influx was 65 nEq/10(8) platelets/hr at pH 7.5 and was more rapid at pH 7.9. About 70% of cell K+ exchanged with plasma in 4 hr with first-order kinetics, while a minor fraction of about 30% exchanged with a slower time course. This slowly exchanging fraction of platelet K+ was thought to arise from heterogeneity in the platelet population. Epinephrine and ADP aggregated gel-filtered platelets and released serotonin, but with loss of only 5%-10% of cell K+ and no beta-glucuronidase. In contrast, thrombin released up to 30% of platelet K+, whether aggregation occurred or was prevented by not stirring the cells. The specific activity of K+ released by all aggregating agents was identical to the specific activity of total platelet K+. Thrombin (0.01-0.2 NIH U/ml) released serotonin and also beta-glucuronidase (an enzyme of the alpha-granule), and there was a linear relation between release of K+ and this enzyme (r = 0.88). No lysis of platelets occurred, since lactic dehydrogenase was not detected. Pretreatment of platelets with aspirin in vitro inhibited thrombin-induced release of serotonin but had no effect on the loss of K+ or beta-glucuronidase. In contrast, the ingestion of aspirin by mouth inhibited the release of serotonin, beta-glucuronidase, and K+ by thrombin. The data suggested that the K+ loss induced by thrombin was primarily derived from release of alpha-granules and that these organelles contained about 20% of the total platelet K+ in a freely exchangeable and nonsequestered state.
 ...
PMID:Potassium uptake and release by human blood platelets. 94 46

It was recently demonstrated that C-reactive protein (CRP)4 inhibits the response of human platelets to heataggregated human gamma-globulin and thrombin and that this inhibition is characterized by a dose-dependent reduction in aggregation, activation of platelet factor 3 (PF3), and release of beta-glucuronidase. In the present experiments, CRP was found also to inhibit the ability of washed human platelets to aggregate in response to poly-L-lysine (PLL); in these experiments, the magnitude of the inhibitory effect was dependent upon the m.w. of PLL used as the stimulating agent, and was more effective with low (15,000 daltons) than with high (400,000 daltons) m.w. polymers. CRP similarly inhibited ADP- and epinephrine-stimulated platelet aggregation in platelet-rich plasma (PRP), and this was characterized by relatively minimal suppression of the primary wave of aggregation. CRP also inhibited the platelet aggregation induced by collagen in PRP, although it had no effect upon the adherence of platelets to collagen. Finally, CRP inhibited the activation of PF3 and the release of serotonin during stimulation of platelets with ADP, and this inhibition was temporally related to the onset of the secondary wave of aggregation. These experiments extend the platelet reactivities inhibited by CRP, show that CRP expresses its inhibitory capacity in platelet-rich plasma as well as upon isolated platelets, raise the possibility that CRP exercises its effects by inhibiting or interfering with the release and/or utilization of endogenous platelet ADP, and support the concept that CRP plays an important role in the control of platelet responsiveness to a variety of stimuli during acute inflammatory reactions.
 ...
PMID:Effects of C-reactive protein on platelet function. II. Inhibition by CRP of platelet reactivities stimulated by poly-L-lysine, ADP, epinephrine, and collagen. 97 42


1 2 3 4 Next >>