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)

The tyrosine kinase inhibitor genistein (5-200 microM) suppressed Ca(2+)-dependent fMLP (1 microM) and ATP (100 microM)-induced release of the lysosomal enzyme, beta-glucuronidase from neutrophil-like HL-60 granulocytes. Agonist-induced Ca2+ mobilization resulted from the release of intracellular Ca2+ stores and the influx of extracellular Ca2+. Genistein (200 microM) suppressed fMLP (1 microM) and ATP (100 microM)-induced Ca2+ mobilization, by 30-40%. Ca2+ release from intracellular stores was unaffected by genistein, however, genistein abolished agonist-induced Ca2+ (Mn2+) influx. Consistent with these findings, genistein (200 microM) or removal of extracellular Ca2+ (EGTA 1 mM), inhibited Ca(2+)-dependent agonist-induced beta-glucuronidase release by similar extents (about 50%). In the absence of extracellular Ca2+, genistein had a small additional inhibitory effect on fMLP and ATP-induced beta-glucuronidase release, suggesting an additional inhibitory site of action. Genistein also abolished store-operated (thapsigargin-induced) Ca2+ (Mn2+) influx. Neither fMLP nor ATP increased the rate of Mn2+ influx induced by thapsigargin (0.5 microM). These data indicate that agonist-induced Ca2+ influx and store-operated Ca2+ influx occur via the same genistein-sensitive pathway. Activation of this pathway supports approximately 50% of lysosomal enzyme release induced by either fMLP or ATP from HL-60 granulocytes.
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PMID:Genistein inhibits lysosomal enzyme release by suppressing Ca2+ influx in HL-60 granulocytes. 1019 61

In a study on the metabolism of flavonoids, the isoflavone genistein was administered orally to rats. Urine samples were collected and treated with beta-glucuronidase and arylsulfatase. Genistein and its metabolites, 4',5,7-trihydroxyisoflavanone (M1), 4',7-dihydroxyisoflavan (M2), and p-ethylphenol (M3) were isolated from the urine following treatment with enzymes. The structures of M1, M2, and M3 were determined on the basis of chemical and spectral data.
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PMID:Urinary metabolites of genistein administered orally to rats. 1172 48

One of the proposed functions of phosphatidic acid (PA) formation from phospholipase D (PLD) activation in neutrophils is to promote degranulation induced by receptor agonists. The present study shows that the time course and dose response of PA formation and degranulation induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP) differed. PLD activation and degranulation also exhibited different dose response to genistein and epigallocatechin gallate (EGCG), inhibitors of protein tyrosine kinases. Genistein inhibited PLD activity with an IC(50) value of 12.2 microM in fMLP- and 107 microM in phorbol myristate acetate (PMA)-stimulated cells. It required higher concentrations of genistein to inhibit degranulation than to inhibit PLD activity induced by fMLP. EGCG in the range of 40-400 microM had no effect on PLD activity but it inhibited the release of beta-glucuronidase and elastase by fMLP-stimulated cells. These results demonstrate differential regulation of PLD activity and degranulation of primary granules by genistein and EGCG in fMLP-stimulated neutrophils.
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PMID:Differential regulation of neutrophil phospholipase d activity and degranulation. 1194 7

The role of beta-glucuronidase in genistein biotransformation was investigated in a human breast cancer MDA-MB-231 xenogeneic athymic mouse model. Genistein combined polysaccharide (GCP), a genistein aglycone rich functional food supplement was used in these experiments. Tumor-bearing mice were subjected to oral administration of GCP for 28 days. GCP treatment significantly inhibited tumor growth. Induction of apoptosis by GCP treatment was related to activation of cleavage of poly(ADP-ribose)polymerase, induction of the p21 protein expression and reduction of cyclin B1 expression in the tumor tissues. Genistein exists as a glucuronide conjugate in normal organ tissues, and the conjugated genistein lacks the physiological activity of the aglycone. Tumor tissues contain large amounts of beta-glucuronidase, the enzyme that converts the genistein beta-glucuronide conjugate into genistein aglycone. The resulting genistein aglycone exerts its chemopreventive activities, including the induction of apoptosis in tumor tissues, and, finally, leads to tumor growth inhibition.
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PMID:Inhibition of human breast cancer growth by GCP (genistein combined polysaccharide) in xenogeneic athymic mice: involvement of genistein biotransformation by beta-glucuronidase from tumor tissues. 1262 3

Numerous physiological processes are regulated by endocrine systems in animals. Endocrine-disrupting chemicals (EDCs) can affect physiological processes of organisms by binding to hormone receptors. Therefore, it is necessary to develop methods for detecting EDCs and removing them from the environment. We have developed a simple and low-cost reporter gene assay system for the comprehensive analysis of estrogenic activity using transgenic Arabidopsis thaliana. This transgenic plant constantly expresses two effector proteins: a chimeric estrogen receptor and a chimeric nuclear receptor coactivator. Estrogen-dependent interaction between the two effector proteins triggers transcriptional activation of reporter gene, beta-glucuronidase. We have demonstrated this transgenic plant's capability of detecting the existence of 17beta-estradiol at a concentration of 50 pM (13 pg/ml) in agar medium. This plant can also detect other estrogenic substances, such as diethylstilbestrol, p-n-nonylphenol, bisphenol A, and Genistein.
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PMID:A simple and extremely sensitive system for detecting estrogenic activity using transgenic Arabidopsis thaliana. 1640 77