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)

Diphosphonates are known to inhibit bone resorption in tissue culture and in experimental animals. This effect may be due to their ability to inhibit the dissolution of hydroxyapatite crystals, but other mechanisms may be important. Since lysosomal enzymes have implicated in the process of bone resorption, we have examined the effect of several phosphonates and of a polyphosphate (P20,2) on lysosomal hydrolases derived from rat liver and rat bone. Dichloromethylene diphosphonate strongly inhibited acid beta-glycerophosphatase (EC 3.1.3.2) and acid p-nitrophenyl phosphatase (EC 3.1.3.2) and to a lesser degree (in descending order) acid pyrophosphatase (EC 3.1.3.-), arylsulfatase A (EC 3.1.6.1), deoxyribonuclease II(EC 3.1.4.6) and phosphoprotein phosphatase (EC 3.1.3.16) of rat liver. Inhibition of acid p-nitrophenyl phosphatase and arylsulfatase A was competitive. Ethane-1-hydroxy-1, 1-diphosphonate did not inhibit any of these enzymes, except at high concentrations. Neither dichloromethylene diphosphonate nor ethane-1-hydroxy-1, 1-diphosphonate had any effect on beta-glucuronidase (EC 3.2.1.31), arylesterase (EC 3.1.1.2) and cathepsin D (EC 3.4.23.5). Of several other phosphonates tested only undec-10-ene-1-hydroxy-1, 1-diphosphonic acid inhibited acid p-nitrophenyl phosphatase strongly, the polyphosphate (P20, I) had little effect. Acid p-nitrophenyl phosphatase in rat calvaria extract behaved in the same way as the liver enzyme and was also strongly inhibited by dichloromethylene diphosphonate, but not by ethane-1-hydroxy-1, 1-diphosphonate. It is suggested that the inhibition of bone resorption by dichloromethylene diphosphonate might be due in part to a direct effect of this diphosphonate on lysosomal hydrolases.
 ...
PMID:The effect of several diphosphonates on acid phosphohydrolases and other lysosomal enzymes. 17 70

Two pathways have been implicated in the regulation of maize ferritin synthesis in response to iron. One of them involves the plant hormone abscisic acid (ABA) and controls the expression of ZmFer2 gene(s). Another pathway, ABA-independent, has been characterized in a de-rooted maize plantlet system and involves an oxidative step. The ZmFer1 maize ferritin gene is not regulated by ABA, and it is shown in this paper that the corresponding mRNA accumulates in de-rooted maize plantlets and BMS (Black Mexican Sweet) maize cell suspension cultures in response to iron via the oxidative pathway described previously. To investigate ZmFer1 gene regulation further, the BMS cell system has been used to develop a transient expression assay using a ZmFer1-beta-glucuronidase fusion. Both iron induction and antioxidant inhibition of ZmFer1 gene expression were observed in this system. Using Northern blot analysis and transient expression experiments, it was shown that both okadaic acid and calyculin A, two serine/ threonine phosphatase inhibitors, specifically inhibit ZmFer1 gene expression. These data indicate that an okadaic acid-sensitive protein phosphatase activity is involved in the regulation of the ZmFer1 ferritin gene in maize cells, and this activity is required for iron-induced expression of this gene.
 ...
PMID:Inhibition of the iron-induced ZmFer1 maize ferritin gene expression by antioxidants and serine/threonine phosphatase inhibitors. 940 24

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 plastid omega-3 fatty acid desaturase (FAD7) catalyzes the conversion of linoleic acid to linolenic acid. Wounding enhances the expression of the FAD7 gene in leaves and induces its expression in stems and roots. The wound-induced expression of the FAD7 promoter was investigated in transgenic tobacco plants carrying the -825 Arabidopsis FAD7 promoter::beta-glucuronidase (GUS) fusion gene. The protein kinase inhibitor, staurosporine, and the protein phosphatase inhibitor, calyculin A, suppressed the wound induction of the FAD7 gene in stems. A tobacco mitogen-activated protein kinase (WIPK) was rapidly activated upon wounding not only in leaves but also in stems and roots, indicating that WIPK probably mediates the wound signals in most vegetative organs. The FAD7 promoter::GUS fusion gene was introduced into the transgenic tobacco plants in which the wipk gene was expressed constitutively at a high level or into the transgenic plants in which the wipk gene was suppressed possibly due to the transgene-induced gene silencing. The wound-induced expression of the FAD7 gene in stems was enhanced in the former transgenic tobacco plants and suppressed in the latter plants. These results suggest that the wound activation of the FAD7 promoter depends on both protein phosphorylation and dephosphorylation events especially in stems, and also that WIPK is involved in such signaling cascades.
 ...
PMID:Possible involvement of protein phosphorylation in the wound-responsive expression of Arabidopsis plastid omega-3 fatty acid desaturase gene. 1081 18

Jasmonates induce plant-defence responses and act to regulate defence-related genes including positive feedback of the lipoxygenase 2 (LOX2) gene involved in jasmonate synthesis. To identify jasmonate-signalling mutants, we used a fusion genetic strategy in which the firefly luciferase (FLUC) and Escherichia coli beta-glucuronidase (GUS) reporters were expressed under control of the jasmonate-responsive LOX2 promoter. Spatial and temporal patterns of reporter expression were determined initially, and revealed that JA-responsive expression from the LOX2 promoter required de novo protein synthesis. Reporter activity was also induced by the protein kinase inhibitor staurosporine and antagonized by the protein phosphatase inhibitor okadaic acid. FLUC bio-imaging, RNA gel-blot analysis and progeny analyses identified three recessive mutants that underexpress the FLUC reporter, designated jue1, 2 and 3, as well as two recessive mutants, designated joe1 and 2, that overexpress the reporter. Genetic analysis indicated that reporter overexpression in the joe mutants requires COI. joe1 responded to MeJA with increased anthocyanin accumulation, while joe2 responded with decreased root growth inhibition. In addition, reporter induction and endogenous LOX2 expression by staurosporine was absent in joe2.
 ...
PMID:Fusion genetic analysis of jasmonate-signalling mutants in Arabidopsis. 1187 72

Agrobacterium tumefaciens transfers DNA to plant cells as a single-stranded DNA molecule (the T-strand) covalently linked to VirD2 protein. VirD2 contains nuclear localization signal sequences that presumably help direct the T-strand to the plant nucleus. We identified a tomato cDNA clone, DIG3, that encodes a protein that interacts with the C-terminal region of VirD2. DIG3 encodes an enzymatically active type 2C serine/threonine protein phosphatase. Overexpression of DIG3 in tobacco BY-2 protoplasts inhibited nuclear import of a beta-glucuronidase-VirD2 nuclear localization signal fusion protein. Thus, DIG3 may be involved in nuclear import of the VirD2 protein and, consequently, the VirD2/transferred DNA complex.
 ...
PMID:Expression of plant protein phosphatase 2C interferes with nuclear import of the Agrobacterium T-complex protein VirD2. 1504 87