Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In microsomes obtained from mouse pancreatic islets, the Mg complex of adenosine 5'-triphosphate (MgATP) increased the dissociation constant (KD) for binding of [3H]glibenclamide by sixfold. In the presence of Mg2+, not only ATP but also adenosine 5'-0-(3-thiotriphosphate) (ATP gamma S), adenosine 5'-diphosphate (ADP), guanosine 5'-triphosphate (GTP), guanosine 5'-diphosphate (GDP), guanosine 5'-0-(3-thiotriphosphate) (GTP gamma S) and guanosine 5'-0-(2-thiodiphosphate) (GDP beta S) inhibited binding of [3H]glibenclamide. These effects were not observed in the absence of Mg2+. Half maximally effective concentrations of the Mg complexes of ATP, ADP, ATP gamma S and GDP were 11.6, 19.0, 62.3 and 90.1 mumol/l, respectively. The non-hydrolyzable analogues adenosine 5'-(beta,gamma-imidotriphosphate) (AMP-PNP) and guanosine 5'-(beta,gamma-imidotriphosphate) (GMP-PNP) did not alter [3H]glibenclamide binding in the presence of Mg2+, MgADP acted much more slowly than MgATP and both MgADP and MgGDP did not inhibit [3H]glibenclamide binding when the concentrations of MgATP and MgGTP were kept low by the hexokinase reaction. Development of MgATP-induced inhibition of [3H]glibenclamide binding and dissociation of [3H]glibenclamide binding occurred at similar rates. However, the reversal of MgATP-induced inhibition of [3H]glibenclamide binding was slower than the association of [3H]glibenclamide with its binding site. Exogenous alkaline phosphatase accelerated the reversal of MgATP-induced inhibition of [3H]glibenclamide binding. MgATP enhanced displacement of [3H]glibenclamide binding by diazoxide. The data suggest that sulfonylureas and diazoxide exert their effects by interaction with the same binding site at the sulfonylurea receptor and that protein phosphorylation modulates the affinity of the receptor.
 ...
PMID:Phosphate and thiophosphate group donating adenine and guanine nucleotides inhibit glibenclamide binding to membranes from pancreatic islets. 190 88

Glucocorticoid(GC)-induced hepatopathy in the dog is characterized by abnormal liver morphology and increases in serum alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), and the liver alkaline phosphatase isoenzyme (LALP) and by the appearance of an unusual isoenzyme of alkaline phosphatase known as the corticosteroid-induced alkaline phosphatase isoenzyme (CALP). It has not been shown whether the increases in serum ALT, GGT, and LALP are as a result of an increase in production of these enzymes or as a result of the GC-induced hepatocellular swelling and possible membrane alterations. Also, it has been assumed that the mechanism of production of CALP is via GC-induced gene derepression and de novo protein synthesis; however, this hypothesis has not been directly tested. Using isolated dog hepatocytes maintained in a confluent monolayer culture in the presence and absence of GC or cyclic AMP, no statistical increase in serum ALT, GGT, or LALP was observed. A combination of GC and cyclic AMP also caused no statistical increase in ALT and GGT; however, we demonstrate that these conditions clearly stimulated the de novo synthesis of LALP. These conditions do not induce the synthesis of CALP as determined by a sensitive immunoassay. The data obtained using this in vitro model suggest that the primary mechanism(s) of the in vivo increase of serum ALT and GGT in GC treated dogs may be other than that of de novo protein synthesis. Likewise, in vitro production of CALP may be a mechanism more complex than the conditions tested in this study.
 ...
PMID:Effect of glucocorticoids on alkaline phosphatase, alanine aminotransferase, and gamma-glutamyltransferase in cultured dog hepatocytes. 197 72

To evaluate ras-mediated signal transduction, an alkaline phosphatase gene (SEAP) was placed under the control of the ras-inducible phorbol ester response element (TRE) in murine fibroblasts (TRE-SEAP cells). The Kirsten ras gene was placed under the control of the glucocorticoid-inducible mouse mammary tumor virus promoter and introduced into the TRE-SEAP cells. Dexamethasone increased ras expression in the TRE-SEAP cells carrying the Kirsten ras gene and stimulated SEAP activity 25-fold. Lavostatin blocked dexamethasone induction of SEAP activity (50% inhibitory concentration, 0.5 microM) but did not affect phorbol ester-induced SEAP activity in the same cells. Lovastatin also did not block forskolin induction of SEAP activity in cells expressing SEAP under the control of the cyclic AMP response element.
 ...
PMID:Lovastatin selectively inhibits ras activation of the 12-O-tetradecanoylphorbol-13-acetate response element in mammalian cells. 200 14

Conditions favouring protein phosphorylation and dephosphorylation are examined for their effects on activity and charge heterogeneity of the rat gastric mucosal histidine decarboxylase. Incubation of gastric supernatant with various combinations of ATP, Mg2+, cyclic AMP and protein kinase under the blockade of endogenous phosphodiesterase and phosphatase fails to alter significantly enzyme activity as assayed with or without pyridoxal 5'-phosphate. Similar results are found with the purified enzyme. No change occurs in the distribution of activity between the charged forms. In contrast, treatment with alkaline phosphatase both inactivates the enzyme with preservation of heterogeneity, full reactivation being achieved by pyridoxal 5'-phosphate, and reduces the number of forms and converts forms II and III to form I with preservation of the catalytic potentialities. The data suggest that the enzyme heterogeneity may be related in part to the phosphorylation state; the possibility that the gastric enzyme is susceptible to several post-translational modifications is discussed.
 ...
PMID:Relationship between the multiple forms of rat gastric histidine decarboxylase: effects of conditions favouring phosphorylation and dephosphorylation. 215 9

Osteoblastic cells were isolated from human maxilla by embedding the bone pieces in collagen gel. The isolated cells could be maintained in monolayer culture up to 50 population doubling levels (PDLs). Both parathyroid hormone (PTH) and prostaglandin E2 (PGE2) increased intracellular cyclic AMP level of the cells. The cells also showed high level of alkaline phosphatase (ALPase) activity and formed mineralized areas in monolayer culture. Electron microscopy demonstrated that these cells were surrounded by numerous well-banded collagen fibrils, among which matrix vesicles were scattered. It was also observed that needle-shaped crystals protruded from some matrix vesicles. These protruded crystals appeared to deposit along the collagen fibrils and a mineralized matrix was formed. The minerals of mineralized matrix mainly consisted of calcium and phosphorus and had the same Ca/P ratio as hydroxyapatite. These results indicate that the cells derived from human bone have characteristics of osteoblastic cells.
 ...
PMID:In vitro mineralization of osteoblastic cells derived from human bone. 215 12

The influence of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on adenylate cyclase responsiveness in cultured osteoblastic cells was studied using a human osteosarcoma cell line SaOS-2. 1,25(OH)2D3 treatment had no effect on cell growth, cell protein and alkaline phosphatase activity. 1,25(OH)2D3 did not alter the basal production of cyclic AMP (cAMP) in intact cells, but the cAMP formation in response to parathyroid hormone (PTH), isoproterenol (ISO) and cholera toxin was attenuated by 1,25(OH)2D3. The response to forskolin, however, was unaffected by 1,25(OH)2D3 treatment. Islet activating protein failed to modify these 1,25(OH)2D3 effect. In cell free experiments, 1,25(OH)2D3 showed similar effect--that is, PTH and ISO-stimulated adenylate cyclase activity were attenuated, but forskolin-stimulated adenylate cyclase was unaffected. 1,25(OH)2D3 treatment had no effect on the kinetics of PTH binding to PTH receptor and on the ADP ribosylation of GTP stimulatory binding protein (Gs) in SaOS-2 cells. According to these results, 1,25(OH)2D3 appeared to change the coupling of Gs with adenylate cyclase, but does not affect receptor, Gs and adenylate cyclase themselves, nor GTP inhibitory binding protein.
 ...
PMID:The effect of 1,25-dihydroxyvitamin D3 on human osteoblast-like osteosarcoma cell: modification of response to PTH. 216 Dec 22

X-ray microanalysis has been used to characterize the enzyme activity hydrolyzing the ATP analogue 5'-adenylylimidodiphosphate (AMP-PNP) in taste bud cells. Rabbit foliate papillae fixed with paraformaldehyde and glutaraldehyde were incubated cytochemically with AMP-PNP as the substrate and lead ion as capture agent. The reaction product which appeared on the microvilli of taste bud cells was examined using an energy dispersive X-ray microanalyzer connected to an analytical electron microscope. The X-ray spectrum thus obtained was compared with that obtained from the product obtained from the demonstration of ATPase activity. Comparison of the phosphorus/lead ratios in the two products showed that twice as much phosphorus was released from an AMP-PNP molecule by the activity in question compared with that released from an ATP molecule by ATPase activity. This indicates that the enzyme hydrolyzes AMP-PNP into AMP and imidodiphosphate and that the enzyme is adenylate cyclase or ATP pyrophosphohydrolase, which possesses a similar hydrolytic property, but not ATPase or alkaline phosphatase, which hydrolyzes AMP-PNP into ADP-NH2 and orthophosphate. This paper provides an example of the use of X-ray microanalysis as a tool for enzyme distinction. The method is applicable to a variety of enzymes and tissues.
 ...
PMID:Identification of 5'-adenylylimidodiphosphate-hydrolyzing enzyme activity in rabbit taste bud cells using X-ray microanalysis. 216 24

The human hepatoma cell line (Li-7A) possesses a high concentration of epidermal growth factor (EGF) receptors and exhibits ectoATPase activity in the presence of either MgATP or CaATP (Knowles: J. Cell. Physiol., 134:109-116, 1988). Growth for 96 hours in the presence of both EGF and cholera toxin or another cyclic AMP elevating agent induced an ectoATPase activity which was more active with CaATP and resistant to inhibition by the sulfydryl reagent, p-chloromercuriphenylsulfonate (pCMPS) (Knowles: Arch. Biochem. Biophys., 263: 264-271, 1988). In contrast, treatment of cells with butyrate, a short chain organic acid which can be derived from the analogue, dibutyryl cyclic AMP, resulted in a 4-7-fold increase of an ectoATPase which was more active with MgATP and highly sensitive to pCMPS inhibition. Maximal induction by butyrate required 48 hours and was dependent on butyrate concentration, but was independent of EGF and cyclic AMP elevating agents. Of six organic acids tested, butyrate was most effective in the induction of the ectoMg2(+)-ATPase. The increase in the ectoMg2(+)-ATPase activity could be prevented with actinomycin D and cycloheximide, indicating that both transcription and translation were necessary for induction. In addition to the induction of the ectoMg2(+)-ATPase, butyrate induced alkaline phosphatase activity, but had no effect on a third ectoenzyme 5'-nucleotidase. These data further support our proposal that two distinct ectoATPases exist in the plasma membrane of Li-7A hepatoma cells.
 ...
PMID:Butyrate induces an ectoMg2(+)-ATPase activity in Li-7A human hepatoma cells. 216 33

We investigated the differentiation-inducing effects of dibutyryl cyclic AMP (dBc AMP) on several cultured osteosarcoma cell lines (DUNN, MOLONEY, OST, FBJ). 1. Cell growth rates of all the osteosarcoma cell lines were reduced by 3mM dBc AMP. 2. Both alkaline phosphatase activity and 45Ca2(+)-uptake were promoted by 3mM dBc AMP. 3. There was, in each cell line except for the OST cells, a marked enlargement of the cell processes under the light microscopic observation. At the electron microscopic level, there were also many findings indicating an increase in cell functions. These results suggest that the differentiation may be induced by cAMP in osteosarcoma cells, and that the differentiation therapy by cAMP-related drugs is promising for a clinical application.
 ...
PMID:[Experimental study on maturational therapy of osteosarcoma cell]. 216 18

We have examined the influence of parathyroid hormone (PTH) and 1,25(OH)2 vitamin D (1,25(OH)2D) on cytoskeletal assembly and biosynthesis in relation with cAMP production and parameters of cell growth and differentiation in normal human osteoblastic cells. Untreated human bone cells showed elongated morphology associated with high levels of actin, vimentin, alpha- and beta-tubulins and alpha-actinin as determined by 2-dimensional-gel electrophoresis and [35S]methionine labelling of cytoskeletal proteins. PTH (20 nM, 24 h) decreased the de novo biosynthesis of vimentin and alpha-actinin in human bone cells, an effect associated with a rise in intracellular cyclic AMP. In addition, PTH induced cytoskeletal disassembly as shown by a 52-70% decrease in the Triton-insoluble fractions of actin, alpha-tubulins and alpha-actinin. 1,25(OH)2D (10 nM, 24 h) also induced a 40-64% decrease in the polymerized fractions of actin, alpha-tubulins and alpha-actinin. These changes were associated with an 83% increase in osteocalcin production. Under these conditions, neither PTH nor 1,25(OH)2D at the doses tested affected alkaline phosphatase activity or cell growth as assessed by [3H]thymidine incorporation into DNA. The results show that PTH and 1,25(OH)2D induce similar inhibition of cytoskeletal proteins assembly involving microfilaments and microtubules in human osteoblastic cells. These alterations of cytoskeletal arrangement in response to PTH and 1,25(OH)2D may contribute to the functional response of human osteoblastic cells to these bone-resorbing hormones.
 ...
PMID:Changes in cytoskeletal proteins in response to parathyroid hormone and 1,25-dihydroxyvitamin D in human osteoblastic cells. 216 75


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