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)

We investigated pulmonary clearance of yttrium (Y) and acute lung injury following intratracheal instillation (i.t.) of yttrium chloride (YCl3) in saline- or YCl3-pretreated rats (30 days before the second challenge). About 67% of the initial dose of Y remained in the lung even 31 days after the i.t. treatment. The pretreatment with YCl3 significantly reduced i.t.-YCl3-induced increases in biochemical inflammatory indicators in bronchoalveolar lavage fluid (BALF), such as lactate dehydrogenase, beta-glucuronidase, and alkaline phosphatase activities and protein concentration, while the pretreatment increased the number of polymorphonuclear leukocyte (PMN) in BALF. These results suggest that the augmentation of PMN infiltration does not play an important role, if any, in i.t. YCl3-induced increases in biochemical indicators in BALF. The reduction of the increases in those biochemical inflammatory indicators may be due, at least in part, to the increase of manganese-superoxide dismutase (Mn-SOD) activity in the lung tissue, because the lung Mn-SOD activity in the YCl3-pretreated group was two times higher than that of the saline-pretreated group.
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PMID:Effects of intratracheal pretreatment with yttrium chloride (YCl3) on inflammatory responses of the rat lung following intratracheal instillation of YCl3. 980 Oct 29

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

Prior work has shown that endocytosis of bovine beta-glucuronidase by human fibroblasts can be mediated by the existence of a Man6P-independent receptor for the recapture and targeting to lysosomes. In this study, we have isolated a peptide (IIIb2) from pronase digested bovine beta-glucuronidase that behaved as competitive inhibitor of the endocytosis of bovine beta-glucuronidase by human fibroblasts. This peptide contained a Ser-X-Ser sequence, where X is probably a posttranslational modified Trp. Antibodies raised against this peptide impaired the endocytosis of the bovine but not the human beta-glucuronidase, implying that the new recognition marker for the endocytosis of acid hydrolases might reside in a single discrete stretch of amino acid sequence. On the other hand, bovine beta-glucuronidase has been shown to bind specifically to receptors of human fibroblast membranes. The binding was saturable, divalent cation-dependent and was competitively inhibited by the IIIb2 peptide, but not by mannose 6-phosphate. Results presented suggested an interplay between manganese concentrations, temperature and pH on the dissociation of the beta-glucuronidase-receptor complexes. All together, these data reinforce the presence of two endocytic systems for the recapture and targeting of beta-glucuronidase in human fibroblasts.
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PMID:Mannose 6-phosphate-independent endocytosis of beta-glucuronidase by human fibroblasts. I. Evidence for the existence of a membrane-binding activity. 1133 85

We identified 18 putative yellow stripe 1 (YS1)-like genes (OsYSLs) in the rice genome that exhibited 36-76% sequence similarity to maize iron(III)-phytosiderophore transporter YS1. Of particular interest was OsYSL2, the transcripts of which were not detected in the roots of either iron-sufficient or iron-deficient plants, but dramatic expression was induced in the leaves by iron deficiency. Based on the nucleotide sequence, OsYSL2 was predicted to encode a polypeptide of 674 amino acids containing 14 putative transmembrane domains. OsYSL2:green fluorescent protein (GFP) was localized in the plasma membrane of onion epidermal cells. Promoter:beta-glucuronidase (GUS) analysis revealed that OsYSL2 was expressed in companion cells in iron-sufficient roots. GUS activity was increased in companion cells, but no GUS staining was observed in epidermal or cortex cells, even in iron-deficient roots. In the leaves and leaf sheaths of iron-sufficient rice, GUS staining was observed in phloem cells of the vascular bundles. In iron-deficient leaves, the OsYSL2 promoter was active in all tissues with particularly strong GUS activity evident in companion cells. The phloem-specific expression of the OsYSL2 promoter suggests that OsYSL2 is involved in the phloem transport of iron. Strong OsYSL2 promoter activity was also detected in developing seeds. Electrophysiological measurements using Xenopus laevis oocytes showed that OsYSL2 transported iron(II)-nicotianamine (NA) and manganese(II)-NA, but did not transport iron(III)-phyosiderophore. These results suggest that OsYSL2 is a rice metal-NA transporter that is responsible for the phloem transport of iron and manganese, including the translocation of iron and manganese into the grain.
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PMID:OsYSL2 is a rice metal-nicotianamine transporter that is regulated by iron and expressed in the phloem. 1525 70

Zinc (Zn) is an essential micronutrient required by all cells but is toxic in excess. We have identified three allelic Zn-sensitive mutants of Arabidopsis (Arabidopsis thaliana). The gene, designated ZINC-INDUCED FACILITATOR1 (ZIF1), encodes a member of the major facilitator superfamily of membrane proteins, which are found in all organisms and transport a wide range of small, organic molecules. Shoots of zif1 mutants showed increased accumulation of Zn but not other metal ions. In combination with mutations affecting shoot-to-root Zn translocation, zif1 hma2 hma4 triple mutants accumulated less Zn than the wild type but remained Zn sensitive, suggesting that the zif1 Zn-sensitive phenotype is due to altered Zn distribution. zif1 mutants were also more sensitive to cadmium but less sensitive to nickel. ZIF1 promoter-beta-glucuronidase fusions were expressed throughout the plant, with strongest expression in young tissues, and predominantly in the vasculature in older tissues. ZIF1 expression was highly induced by Zn and, to a lesser extent, by manganese. A ZIF1-green fluorescent protein fusion protein localized to the tonoplast in transgenic plants. MTP1 has been identified as a tonoplast Zn transporter and a zif1-1 mtp1-1 double mutant was more sensitive to Zn than either of the single mutants, suggesting ZIF1 influences a distinct mechanism of Zn homeostasis. Overexpression of ZIF1 conferred increased Zn tolerance and interveinal leaf chlorosis in some transgenic lines in which ZIF1 expression was high. We propose that ZIF1 is involved in a novel mechanism of Zn sequestration, possibly by transport of a Zn ligand or a Zn ligand complex into vacuoles.
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PMID:A novel major facilitator superfamily protein at the tonoplast influences zinc tolerance and accumulation in Arabidopsis. 1727 87

Calcium (Ca) and manganese (Mn) are essential nutrients required for normal plant growth and development, and transport processes play a key role in regulating their cellular levels. Arabidopsis (Arabidopsis thaliana) contains four P(2A)-type ATPase genes, AtECA1 to AtECA4, which are expressed in all major organs of Arabidopsis. To elucidate the physiological role of AtECA2 and AtECA3 in Arabidopsis, several independent T-DNA insertion mutant alleles were isolated. When grown on medium lacking Mn, eca3 mutants, but not eca2 mutants, displayed a striking difference from wild-type plants. After approximately 8 to 9 d on this medium, eca3 mutants became chlorotic, and root and shoot growth were strongly inhibited compared to wild-type plants. These severe deficiency symptoms were suppressed by low levels of Mn, indicating a crucial role for ECA3 in Mn nutrition in Arabidopsis. eca3 mutants were also more sensitive than wild-type plants and eca2 mutants on medium lacking Ca; however, the differences were not so striking because in this case all plants were severely affected. ECA3 partially restored the growth defect on high Mn of the yeast (Saccharomyces cerevisiae) pmr1 mutant, which is defective in a Golgi Ca/Mn pump (PMR1), and the yeast K616 mutant (Deltapmc1 Deltapmr1 Deltacnb1), defective in Golgi and vacuolar Ca/Mn pumps. ECA3 also rescued the growth defect of K616 on low Ca. Promoter:beta-glucuronidase studies show that ECA3 is expressed in a range of tissues and cells, including primary root tips, root vascular tissue, hydathodes, and guard cells. When transiently expressed in Nicotiana tabacum, an ECA3-yellow fluorescent protein fusion protein showed overlapping expression with the Golgi protein GONST1. We propose that ECA3 is important for Mn and Ca homeostasis, possibly functioning in the transport of these ions into the Golgi. ECA3 is the first P-type ATPase to be identified in plants that is required under Mn-deficient conditions.
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PMID:ECA3, a Golgi-localized P2A-type ATPase, plays a crucial role in manganese nutrition in Arabidopsis. 1802 60

Some new complexes of mefenamic acid with potentially interesting biological activity are described. The complexes of mefenamic acid [Mn(mef)(2)(H(2)O)(2)], 1, [Co(mef)(2)(H(2)O)(2)], 2, [Ni(mef)(2)(H(2)O)(2)], 3, [Cu(mef)(2)(H(2)O)](2), 4 and [Zn(mef)(2)], 5, were prepared by the reaction of mefenamic acid, a potent anti-inflammatory drug with metal salts. Optical and infrared spectral data of these new complexes are reported. Monomeric six-coordinated species were isolated in the solid state for Mn(II), Ni(II) and Co(II), dimeric five-coordinated for Cu(II) and monomeric four-coordinated for Zn(II). In DMF or CHCl(3) solution the coordination number is retained and the coordinated molecules of water are replaced by solvent molecules. The anti-oxidant properties of the complexes were evaluated using the 1,1-diphenyl-2-picrylhydrazyl, DPPH, free radical scavenging assay. The scavenging activities of the complexes were measured and compared with those of the free drug and vitamin C. We have explored their ability to inhibit soybean lipoxygenase, beta-glucuronidase and trypsin- induced proteolysis. The complex [Mn(mef)(2)(H(2)O)(2)] exhibits the highest antioxidant activity and the highest inhibitory effect against the soybean lipogygenase (LOX), properties that are not demonstrated by mefenamic acid. Their inhibitory effects on rat paw edema induced by Carrageenan was studied and compared with those of mefenamic acid. The complex [Zn(mef)(2)] exhibited a strong inhibitory effect at 0.1 mmol/Kg B.W. (81.5 +/- 1.3% inhibition), superior to the inhibition induced by mefenamic acid at the same dose (61.5 +/- 2.3% inhibition). Mefenamic acid and its metal complexes have been evaluated for antiproliferative activity in vitro against the cells of three human cancer cell lines: MCF-7 (human breast cancer cell line), T24 (bladder cancer cell line), A-549 (non-small cell lung carcinoma) and a mouse fibroblast L-929 cell line. The copper(II) complex displays against T24, MCF-7 and L-929 cancer cell lines, IC(50) values in a microM range similar to that of the antitumor drug cis-platin and they are considered for further stages of screening in vitro and/or in vivo as agents with potential antitumor activity.
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PMID:Anti-oxidant, in vitro, in vivo anti-inflammatory activity and antiproliferative activity of mefenamic acid and its metal complexes with manganese(II), cobalt(II), nickel(II), copper(II) and zinc(II). 1872 Jan 91


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