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

---

Query: EC:3.2.1.31 (beta-glucuronidase)
7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Polymorphonuclear leukocytes (PMN) may contribute to the pathogenesis of acute coronary heart disease (CHD). 2. Epidemiological and laboratory evidence suggests that red wine, by virtue of its polyphenolic constituents, may be more effective than other alcoholic beverages in reducing the risk of CHD mortality. 3 The aim of the present study was to investigate the effects of trans-resveratrol (3,4',5-trihydroxy-trans-stilbene), a polyphenol present in most red wines, on functional and biochemical responses of PMN, upon in vitro activation. 4. trans-Resveratrol exerted a strong inhibitory effect on reactive oxygen species produced by PMN stimulated with 1 microM formyl methionyl leucyl phenylalamine (fMLP) (IC50 1.3+/-0.13 microM, mean+/-s.e.mean), as evaluated by luminol-amplified chemiluminescence. 5. trans-Resveratrol prevented the release of elastase and beta-glucuronidase by PMN stimulated with the receptor agonists fMLP (1 microM, IC50 18.4+/-1.8 and 31+/-1.8 microM), and C5a (0.1 microM, IC50 41.6+/-3.5 and 42+/-8.3 microM), and also inhibited elastase and beta-glucuronidase secretion (IC50 37.7+/-7 and 25.4+/-2.2 microM) and production of 5-lipoxygenase metabolites leukotriene B4 (LTB4), 6-trans-LTB4 and 12-trans-epi-LTB4 (IC50 48+/-7 microM) by PMN stimulated with the calcium ionophore A23187 (5 microM). 6. trans-Resveratrol significantly reduced the expression and activation of the beta2 integrin MAC-1 on PMN surface following stimulation, as revealed by FACS analysis of the binding of an anti-MAC-1 monoclonal antibody (MoAb) and of the CBRM1/5 MoAb, recognizing an activation-dependent epitope on MAC-1. Consistently, PMN homotypic aggregation and formation of mixed cell-conjugates between PMN and thrombin-stimulated fixed platelets in a dynamic system were also prevented by transresveratrol. 7. These results, indicating that trans-resveratrol interferes with the release of inflammatory mediators by activated PMN and down-regulates adhesion-dependent thrombogenic PMN functions, may provide some biological plausibility to the protective effect of red wine consumption against CHD.
...
PMID:Effect of trans-resveratrol, a natural polyphenolic compound, on human polymorphonuclear leukocyte function. 960 77

The immunosuppressive drug cyclosporin A (CsA) depresses neutrophil oxidative burst which may lead to an increased susceptibility to infection in transplant patients. Using specific CsA analogues we investigated the mechanism of inhibition of the oxidative burst and evaluated short and long-term effects of CsA on dimethylsulphoxide-differentiated HL-60 neutrophils. A biphasic pattern was observed: a 4 h pre-treatment with CsA (1 microM) diminished the fMLP induced [Ca2+]c rise, reactive oxygen species (ROS) production, and beta-glucuronidase release by about 40%, whereas a 20 h pre-treatment increased these responses by about 1.5 fold. [MeVal4]CsA, which binds with high affinity to cyclophilin but inhibits the interaction of the CsA-cyclophilin complex with calcineurin, blocked the stimulation observed with CsA after a 20 h incubation but did not alter the CsA effects after a 4 h pre-treatment. PSC 833 (1 microM), a potent multi drug resistance transporter (MDR) inhibitor, diminished ROS production to the same extent as a 4 h CsA incubation but was ineffective after a 20 h pre-treatment. An involvement of MDR as a basis for CsA or PSC 833 action was ruled out based on the results of the calcein retention assay. [3H]CsA uptake showed that CsA and [MeVal4]CsA, but not CsH or PSC 833 were strongly taken up and retained by the cells. In conclusion, the reduction of the responses after 4 h appear to be due to a primary reduction of calcium signalling, while the enhanced responses after 20 h may be due to calcineurin inhibition.
...
PMID:Biphasic effects of cyclosporin A on formyl-methionyl-leucyl-phenylalanine stimulated responses in HL-60 cells differentiated into neutrophils. 975 96

The differentiation of chloroplasts into chromoplasts involves a series of biochemical changes that culminate with the intense accumulation of long chain chromophore carotenoids such as lycopene, rhodoxanthin, astaxanthin, anhydroeschsoltzxanthin, capsanthin, and capsorubin. The signal pathways mediating these transformations are unknown. Chromoplast carotenoids are known to accumulate in green tissues experiencing stress conditions, and studies indicate that they provide efficient protection against oxidative stress. We tested the role of reactive oxygen species (ROS) as regulators of chromoplast carotenoid biosynthesis in vivo. The addition of ROS progenitors, such as menadione, tert-butylhydroperoxide, or paraquat and prooxidants such as diamide or buthionine sulfoximine to green pericarp discs of pepper fruits rapidly and dramatically induce the simultaneous expression of multiple carotenogenic gene mRNAS that give rise to capsanthin. Similarly, down-regulation of catalase by amitrole induces expression of carotenogenic gene mRNAs leading to the synthesis of capsanthin in excised green pericarp discs. ROS signals from plastids and mitochondria also contribute significantly to this process. Analysis of the capsanthin-capsorubin synthase promoter in combination with a beta-glucuronidase reporter gene reveals strong activation in transformed pepper protoplasts challenged with the above ROS. Collectively these data demonstrate that ROS act as a novel class of second messengers that mediate intense carotenoid synthesis during chromoplast differentiation.
...
PMID:Induction and control of chromoplast-specific carotenoid genes by oxidative stress. 980 38

The plant defensin PDF1.2 has previously been shown to accumulate systemically via a salicylic acid-independent pathway in leaves of Arabidopsis upon challenge by fungal pathogens. To further investigate the signalling and transcriptional processes underlying plant defensin induction, a DNA fragment containing 1184 bp and 1232 bp upstream of the transcriptional and translational start sites, respectively, was cloned by inverse PCR. To test for promoter activity this DNA fragment was linked to the beta-glucuronidase (GUS)-encoding region of the UidA gene as a translational fusion and introduced into Arabidopsis ecotype C-24. Challenge of the transgenic plants with the fungal pathogens Alternaria brassicicola and Botrytis cinerea resulted in both local and systemic induction of the reporter gene. Wounding of the transgenic plants had no effect on GUS activity. Treatment of the transgenic plants with either jasmonates or the active oxygen generating compound paraquat strongly induced the reporter gene. In contrast, neither salicylate nor its functional analogues 2,6-dichloroisonicotinic acid and 1,2,3-benzothiodiazole-7-carbothioic acid S-methyl ester resulted in reporter gene induction. These results are consistent with the existence of a salicylic acid-independent signalling pathway, possibly involving jasmonates as regulators, that is triggered by pathogen challenge but not by wounding. The transgenic plants containing the PDF1.2-based promoter-reporter construct will provide useful tools for future genetic dissection of this novel systemic signalling pathway.
...
PMID:The promoter of the plant defensin gene PDF1.2 from Arabidopsis is systemically activated by fungal pathogens and responds to methyl jasmonate but not to salicylic acid. 986 13

Previously, it was found that patients with necrotizing crescentic glomerulonephritis (NCGN) and anti-neutrophil cytoplasmic autoantibodies (ANCA) directed against proteinase 3 (anti-PR3) had a faster deterioration of renal function and more active renal vasculitic lesions than patients with ANCA directed against myeloperoxidase (anti-MPO). Because ANCA-mediated neutrophil activation is thought to play an important role in the pathophysiology of this form of glomerulonephritis, this study was conducted to determine whether anti-PR3 are capable of inducing a more pronounced activation of neutrophils in vitro than anti-MPO. To test this hypothesis, the release of reactive oxygen radicals, as assessed by ferricytochrome c reduction and by dihydrorhodamine 123 oxidation, and the release of granule constituents from healthy donor neutrophils upon stimulation with IgG fractions were measured from 17 anti-PR3- and 14 anti-MPO-positive patients with active NCGN. Patients with anti-PR3 had a higher renal activity index (P < 0.05) compared with patients with anti-MPO. IgG fractions from anti-PR3-positive patients induced more oxygen radical release from tumor necrosis factor-alpha-primed neutrophils compared with IgG fractions from anti-MPO-positive patients, as assessed by ferricytochrome c reduction (P < 0.05) and dihydrorhodamine 123 oxidation (P < 0.01). In addition, IgG fractions from anti-PR3-positive patients generated more neutrophil degranulation of beta-glucuronidase (P < 0.01) than IgG fractions from anti-MPO-positive patients. In conclusion, IgG fractions from anti-PR3-positive patients with NCGN are more potent activators of the respiratory burst and degranulation in vitro than IgG fractions from anti-MPO-positive patients. These observations may be relevant in view of the clinical differences between anti-PR3- and anti-MPO-positive patients with NCGN.
...
PMID:In vitro neutrophil activation by antibodies to proteinase 3 and myeloperoxidase from patients with crescentic glomerulonephritis. 1040 6

The lipophilic aglycone 5,7-dihydroxy-3,8-dimethoxyflavone (gnaphalin) isolated from the aerial flowering parts of Helichrysum picardii Boiss. & Reuter (Asteraceae) was tested for interactions with the cyclo-oxygenase and 5-lipoxygenase pathways of arachidonate metabolism in stimulated rat peritoneal leukocytes, and for its effects on leukocyte granular enzyme release, cell viability and interactions with reactive oxygen species. Gnaphalin dose-dependently inhibited generation of the cyclo-oxygenase metabolite thromboxane B2 (IC50 = 39.9 +/- 3.9 microM), and of the 5-lipoxygenase metabolite leukotriene B4, although the potency was two-fold less (IC50 = 81.8 +/- 12.9 microM). At concentrations of 6 to 320 microM, gnaphalin did not affect secretion of the pro-inflammatory enzymes lysozyme, myeloperoxidase and beta-glucuronidase from the neutrophil secretory granules, and did not scavenge hydrogen peroxide or hypochlorous acid. However, gnaphalin effectively scavenged superoxide radicals generated in the hypoxanthine/xanthine oxidase system (IC50 = 40 microM) and by PMA-stimulated leukocytes (> 60% at 500 microM), directly inhibited xanthine oxidase (85% at 395 microM) and inhibited Fe(3+)-ascorbate-induced liposomal peroxidation (IC50 = 215 microM). Thus, like some other flavonoids found in medicinal herbs, gnaphalin possesses an array of potentially beneficial anti-eicosanoid and free-radical scavenging properties which may alongside other constituents contribute to the claimed medicinal properties of the plant from which it is derived.
...
PMID:Inhibition of leukocyte eicosanoid generation and radical scavenging activity by gnaphalin, a lipophilic flavonol isolated from Helichrysum picardii. 1048 68

In plants, light is not only an energy source but also a very important signal that modulates development and differentiation. Here, we report a putative photo-regulatory factor sequence in LKP1 (LOV kelch protein 1). LKP1 cDNA encodes a protein of 610 amino acids and with a molecular weight of 65 905 with an LOV domain and kelch repeats. LOV domains are present in a number of sensor proteins involved in the detection of light, oxygen or voltage. The LKP1 LOV is very similar to the LOV domains in NPH1, a plasma membrane-associated blue light receptor kinase that regulates phototropism (Huala, E., Oeller, P.W., Liscum, E., Han, I-S., Larsen, E. & Briggs, W.R. (1997) Science, 278, 2120-2123). LKP1 mRNA accumulates in roots, stems, flowers and siliques. It is most abundant in leaves, and least abundant in seeds. Transgenic plants with a beta-glucuronidase (GUS) reporter gene driven by a 1.5 kb LKP1 promoter display strong GUS activity in leaves. Transgenic plants with a 35S:LKP1 cDNA gene overexpress LKP1 mRNA. These plants have elongated hypocotyls and petioles with elongated cells, and exhibit distinct cotyledon movement during the day. Expression of 35S:LKP1 in transgenic Arabidopsis promotes late flowering in plants grown under long-day, but not under short-day conditions. Vernalization does not affect the late flowering phenotype of the 35S:LKP1 plants. Transgenic plants possessing the 35S:GFP-LKP1 construct also have long hypocotyles and petioles, and a late flowering phenotype, suggesting that the GFP-LKP1 fusion protein is active. The GFP-associated fluorescence in 35S:GFP-LKP1 plants is observed in nuclei and cytosol, indicating that LKP1 is a new nucleo-cytoplasmic factor that influences flowering time in the long day pathway of Arabidopsis.
...
PMID:LKP1 (LOV kelch protein 1): a factor involved in the regulation of flowering time in arabidopsis. 1099 91

In order to improve current chemotherapeutic treatment and diminish severe side effects, several prodrug strategies have evolved to achieve site-specific delivery of cytotoxic anticancer agents. This review concentrates on recent developments of antitumor prodrug monotherapy with prodrugs that are designed for direct recognition of tumor-associated factors, such as hypoxia, tumor-associated enzymes and receptors. Firstly, oxygen deficiency in the core of solid tumors leads to enhanced activity of reducing enzymes, like for example nitroreductases, which can be used for site- specific conversion of prodrug to drug. Secondly, some enzymes are present in elevated levels in tumor tissue: beta-glucuronidase leaks from necrotic areas within tumors, while tumor cells for invasive and metastatic activities need several tumor-associated proteases, like plasmin. These enzymes form an attractive target for designing selective prodrugs. Finally, tumor-selective expression of receptors can be exploited for the delivery of antitumor agents. Low molecular weight binding motifs for these receptors can be coupled to cytotoxic drugs in order to obtain tumor-homing conjugates. At present, receptor-binding motifs for a number of receptors that are required for angiogenesis are used for prodrug monotherapy. There exists an increasing body of literature, which describes the complex interplay not only between tumor-associated enzymes, but also between these enzymes and tumor-associated receptors in the process of tumor invasion and metastasis, indicating the feasibility of targeting cytotoxic drugs to these key players in tumor growth. This paper reviews the development and evaluation of anticancer prodrugs, and their application in the various prodrug monotherapy approaches.
...
PMID:Anticancer prodrugs for application in monotherapy: targeting hypoxia, tumor-associated enzymes, and receptors. 1147 43

An Azospirillum brasilense Sp7 strain containing a plasmid-borne translational cytN-gusA fusion was grown in a continuous culture to quantitatively evaluate the influence of extracellular signals (such as O(2)) on expression of the cytNOQP operon. The dissolved oxygen concentration was shifted at regular time intervals before the steady state was reached. The measured beta-glucuronidase activity was used to monitor cytN gene expression. However, as the beta-glucuronidase activity in the experimental setup not only depended on altered transcription of the hybrid gene when the signal was varied but was also influenced by cellular accumulation, degradation, and dilution of the hybrid fusion protein, a mathematical method was developed to describe the intrinsic properties of the dynamic bioprocess. After identification and validation of the mathematical model, the apparent specific rate of expression of the fusion, which was independent of the experimental setup, could be deduced from the model and used to quantify gene expression regulated by extracellular environmental signals. In principle, this approach can be generalized to assess the effects of external signals on bacterial gene expression.
...
PMID:Quantitative analysis of bacterial gene expression by using the gusA reporter gene system. 1147 3

A tetrapeptide derivative PEP1261 [Boc-Lys-(Boc)-Arg-Asp-Ser-(tBu)-OtBu], corresponding to residues 39-42 of human lactoferrin, was tested for its antiinflammatory action in adjuvant induced arthritis in rats. Administration of heat killed Mycobacterium tuberculosis (500 microg/0.1 ml of paraffin oil) intradermally into the foot pad of right hind paw resulted in an increased paw volume and an increase in the levels of reactive oxygen species and beta-glucuronidase as well as a decrease in the antioxidants levels. PEP1261, at an effective dose of 10 mg/kg body wt., exhibited a significant antiarthritic activity as evidenced by lowering of paw volume and inhibited the free radicals toxicity by increasing the antioxidants levels. This peptide derivative was also shown to have a membrane stabilizing action by significantly decreasing the total and free activity of beta-glucuronidase and inhibiting the rate of release of the enzyme from lysosomal rich fraction. Histopathological studies confirmed the above results by showing a decrease in mononuclear cell infiltration, hypertrophy, hyperplasia and pannus formation after PEP1261 treatment in arthritic rats.
...
PMID:A novel peptide derivative exhibits anti inflammatory and antioxidant activity in adjuvant induced arthritis in rats. 1193 51


<< Previous 1 2 3 4 5 6 7 8 9 10

---