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

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Query: EC:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glucocorticoid receptors in cytosol preparations from rat liver or mouse L cells are inactivated by phospholipase A2 or calf intestine alkaline phosphatase. Molybdate ion, an inhibitor of a variety of phosphatase enzymes, does not prevent inactivation of glucocorticoid binding capacity by alkaline phosphatase but it blocks inactivation by phospholipase A2. In neither case is the enzyme itself inhibited, and the effect of molybdate on phospholipase-mediated inactivation appears to reflect the ability of molybdate to prevent receptor inactivation by the detergent action of lysophosphatides.
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PMID:Glucocorticoid receptor stabilization: relative effects of molybdate ion on inactivation by alkaline phosphatase and phospholipase A2. 686 2

Lysosomal catabolism of radioactively labelled phosphatidylethanolamine, phosphatidylcholine and several potential metabolites of these diacylphospholipids was studied using rat-liver lysosomes which had been isolated from Triton WR-1339-treated animals. Hydrolysis of these lipids seems to be restricted to the soluble lysosomal compartment. The initial intralysosomal degradation is predominantly catalysed by phospholipase A1 (EC 3.1.1.32) followed by lysophospholipase (EC 3.1.1.5). The end products of this pathway are free fatty acids and glycerophosphorylethanolamine or glycerophosphorylcholine. These phosphodiesters are not hydrolysed further in lysosomes, as has been shown previously (Fowler, S. and De Duve, C. (1969) J. Biol. Chem. 144, 471-481). The intermediary lysophospholipids, however, are also hydrolysed by an alternative pathway, i.e. by a lysophospholipase which catalyses the hydrolysis of the glycerophosphate ester bond, followed by a monoacylglycerol lipase and a phosphomonoesterase (EC 3.1.3.2), respectively. Besides these two catabolic routes of intralysosomal hydrolysis of phosphatidylethanolamine and phosphatidylcholine, additional pathways are possible, which seem, however, to be of minor importance, at least in the substrate concentration ranges employed in these studies. These additional reactions include attack by a phospholipase A2 (EC 3.1.1.4) and--as discovered recently (Matsuzawa, Y. and Hostetler, K.Y. (1980) J. Biol. Chem. 255, 646-652)--by a phospholipase C (EC 3.1.4.3). Cations such as Mg2+, Ca2+, K+ and Na+ inhibit preferentially deacylation reactions.
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PMID:Hydrolytic degradation of phosphatidylethanolamine and phosphatidylcholine by isolated rat-liver lysosomes. 706 64

Critical events in the adaptation of osseous tissues to implant materials involve initial calcification of the newly synthesized bone. Previous studies indicated that bone-bonding but not nonbonding glass ceramics increase the matrix vesicle number, thereby compensating for delayed maturation of the extracellular organelles. The present study assessed whether this was also true for metal implants commonly used in orthopaedics and oral medicine. Bone-bonding titanium (Ti) or nonbonding stainless steel (SS) implants were placed in the right tibias of Sabra rats following ablation of the marrow. At 3, 6, 14, and 21 days postinjury, newly formed endosteal bone in the treated and contralateral limbs was removed and matrix vesicle-enriched membranes isolated. Alkaline phosphatase and phospholipase A2 specific activities and phosphatidylserine (PS) content were determined and compared with those of a nonsurgical control group. Results show that matrix vesicle alkaline phosphatase and phospholipase A2 activity and PS content was increased in the Ti-implanted limbs at 6 (peak), 14, and 21 days, although at levels less than observed in normal healing. Alkaline phosphatase activity remained elevated throughout the healing period. In contrast, these parameters were markedly inhibited in the SS-implanted limbs with respect to Ti or to normal healing. Both implants altered the systemic response associated with marrow ablation, but in an implant-specific manner. The results support the hypothesis that cells adjacent to bone-bonding materials can compensate for negative effects on primary mineralization during osteogenesis, whereas cells adjacent to nonbonding materials either do not compensate or are further depressed. The data support the use of the rat marrow ablation model as a tool for rapid, initial assessment of biomaterials in bone.
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PMID:Markers of primary mineralization are correlated with bone-bonding ability of titanium or stainless steel in vivo. 766 63

Venoms from two related Australian ants, a jumper ant (Myrmecia pilosula) and a bulldog ant (Myrmecia pyriformis), were quantitatively analysed for the following enzymic activities: phospholipase A2, phospholipase B, phospholipase C, hyaluronidase, esterase, acid phosphatase, alkaline phosphatase and phosphodiesterase. Both venoms contained phospholipase A2, phospholipase B, hyaluronidase, acid phosphatase and alkaline phosphatase activities. Myrmecia pyriformis venom had significantly greater phospholipase B, acid phosphatase and alkaline phosphatase activities than Myrmecia pilosula venom. No detectable quantities of phospholipase C, esterase or phosphodiesterase activities were found in either venom.
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PMID:Some enzymic activities of two Australian ant venoms: a jumper ant Myrmecia pilosula and a bulldog ant Myrmecia pyriformis. 772 23

Recent evidence suggests that phospholipase A2 (PLA2)-derived lipid mediators may regulate a number of neutrophil responses including degranulation and adhesion. In view of the potential role of PLA2 in stimulus-secretion coupling, we examined the relationship between PLA2 activation and the surface expression of CD11b/CD18 (MAC-1) in human polymorphonuclear leukocytes (hPMNL), including the functional consequences of PLA2 inactivation on MAC-1-dependent adhesion. The selective inhibition of PLA2 by the marine natural products manoalide (MLD) and scalaradial (SLD) blocks [3H]arachidonic acid (AA) release in calcium ionophore A23187-stimulated neutrophils, and also inhibits secretion of specific and azurophilic granule constituents. Additional studies demonstrate that MLD, SLD, and other less potent PLA2 inhibitors such as 4-bromophenacylbromide and nordihydroguiaretic acid inhibit the surface expression of MAC-1 (IC50: MLD, 0.33 microM; SLD, 0.23 microM; 4-bromophenacylbromide, 2.8 microM; NDGA, 3.5 microM) at concentrations similar to those at which they inhibit [3H]AA release. Inhibitors of cyclooxygenase, 5-lipoxygenase, protein kinase C, or calcium channel antagonists have no effect on MAC-1 expression. PLA2 inactivation also prevents MAC-1 up-regulation in hPMNL stimulated with FMLP, IL-8, TNF-alpha, PMA, or platelet activating factor. In FMLP-stimulated hPMNL, under conditions in which no secondary granule constituents are secreted, MAC-1 and alkaline phosphatase up-regulation from intracellular granules is inhibited by MLD and SLD. Functional assays also demonstrate that MLD and SLD block MAC-1-dependent adhesion of activated neutrophils to keyhole limpet hemocyanin at concentrations that block the surface expression of MAC-1. [3H]AA release and MAC-1 expression in MLD and SLD-treated hPMNL could be recovered in the presence of 1 mM hydroxylamine in a time-dependent fashion, consistent with reported data that MLD and SLD inactivate PLA2 through Schiff base formation. In summary, these data emphasize the role of PLA2 as a key regulator of MAC-1 expression in models of neutrophil adhesion.
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PMID:Regulation of CD11b/CD18 expression in human neutrophils by phospholipase A2. 822 53

To determine whether rat osteoblasts synthesize proteins of the annexin family and to evaluate the extent to which glucocorticoids modulate the expression of annexins by these cells, osteoblasts were grown in primary cultures in the absence or presence of dexamethasone, and the expression of annexins was evaluated by immunoblotting using polyclonal antibodies against human annexins. Four different annexins (I, II, V, and VI) were found to be expressed by rat osteoblasts. The expression of annexin I, but not the other annexins studied, was increased in osteoblasts cultured in the presence of dexamethasone (173 +/- 33% increase comparing untreated cells and cells treated for 10 days with 5 x 10(-7) M dexamethasone). Increased expression of annexin I was observed after the third day of exposure to dexamethasone and rose thereafter until day 10; annexin I expression increased with dexamethasone concentrations above 10(-10) M throughout the range of concentrations studied. The increase in annexin I protein was associated with an increase in annexin I mRNA and was completely blocked by the concomitant addition of the glucocorticoid receptor antagonist RU 38486. The increase in annexin I content following dexamethasone treatment was associated with an increase in alkaline phosphatase activity and PTH-induced cAMP stimulation, whereas phospholipase A2 activity in the culture medium was reduced to undetectable levels. The finding that four annexins are expressed in rat osteoblasts in primary culture raises the possibility that these proteins could play an important role in bone formation by virtue of their ability to bind calcium and phospholipids, serve as Ca2+ channels, interact with cytoskeletal elements, and/or regulate phospholipase A2 activity. In addition, the dexamethasone-induced increase in annexin I may represent a mechanism by which glucocorticoids modify osteoblast function.
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PMID:Expression of annexin I, II, V, and VI by rat osteoblasts in primary culture: stimulation of annexin I expression by dexamethasone. 825 57

The effect of 40- to 60-mesh hydroxyapatite (HA) granules (Calcitek, Inc., Carlsbad, CA) on the process of primary mineralization during bone healing was examined following insertion of the HA granules into rat tibial bone after marrow ablation. Response to HA was assessed by monitoring morphometric and biochemical changes in matrix vesicles, which are extracellular organelles associated with initial calcification. Following insertion of HA, matrix vesicle-enriched membranes (MVEMs) were isolated from the tissue adjacent to the implant and from the endosteum of the contralateral limb at 3, 6, 14, and 21 days and from a nonimplanted control group (t = 0). MVEM alkaline phosphatase- and phospholipase A2-specific activities were increased on days 6 (peak) and 14; phosphatidylserine content was also elevated on days 6 and 14 (peak). Comparable changes were seen in the contralateral limb but at lesser magnitudes. Morphological changes were observed as well. The number of matrix vesicles/micron2 matrix increased on days 6 (peak) and 14. The mean diameter of the matrix vesicles was elevated on days 6 (peak), 14, and 21. Mean distance from the calcifying front increased on day 6 but was decreased on days 14 and 21. These results indicated that HA behaves like bone-bonding implants in that there is a stimulation of matrix vesicle enzymes, increased phosphatidylserine content, and increase numbers of matrix vesicles. However, the increases occur only after 6 days postimplantation, indicating a delay in response when compared to normal healing. This delay is confirmed by the morphometric measurements. HA causes a reduction in the response associated with marrow ablation. In addition, the effects of HA are comparable locally and systemically but with different intensity. These observations suggest that osteogenic cells are able to compensate for the inhibitory effects of HA and primary calcification involves normal matrix vesicle production and maturation, if somewhat delayed and reduced in magnitude. The ability to support primary mineral formation may contribute to the successful bonding of HA with surrounding osseous tissue.
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PMID:Effects of hydroxyapatite implants on primary mineralization during rat tibial healing: biochemical and morphometric analyses. 840 15

Chondrocytes in the endochondral differentiation pathway produce transforming growth factor-beta (TGF-beta) and response to this growth factor both in vitro and in vivo. To clarify the role that cell maturation state plays in the response, we used a well characterized chondrocyte cell culture model which compares cartilage cells at two different stages of maturation. Confluent fourth passage cultures of rat costochondral resting zone and growth zone cartilage cells were incubated with recombinant human (rh) TGF-beta-1 for 24, 48, or 72 h, and the effect on cell number and [3H]thymidine incorporation was observed. To assess whether TGF-beta regulates chondrocyte differentiation to a calcifying cartilage phenotype, cells were incubated for 24 h with TGF-beta, and the specific activities of alkaline phosphatase and phospholipase A2, two enzymes associated with calcification, were assayed in isolated plasma membranes and matrix vesicles. Alkaline phosphatase-specific activity was also measured in the cell layer. Modulation of TGF-beta action by vitamin D metabolites, also known to regulate endochondral differentiation, was examined. The ability of the chondrocytes to produce latent TGF-beta was assayed. The results show that: 1) quiescent chondrocytes at two stages of endochondral maturation respond to rhTGF-beta-1 by increasing [3H]thymidine incorporation; 2) growth zone cells exhibit no increase in cell number over a 72-h incubation with TGF-beta, whereas resting zone cells exhibit a dose-dependent increase in cell number at 72 h; 3) nonquiescent cells exhibit an increase in alkaline phosphatase-specific activity at 24 h; 4) the effects on this membrane enzyme are comparable in the plasma membranes and matrix vesicles, but the net effect is greater in the extracellular organelle due to the intrinsically higher levels of activity; 5) although differentiation is promoted in resting zone cells, it is limited in the growth zone cells by inhibition of phospholipase A2 activity; and 6) there is a synergistic enhancement of resting zone chondrocyte differentiation when cells are exposed to rhTGF-beta-1 and 24,25-dihydroxyvitamin D3.
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PMID:Direct effects of transforming growth factor-beta on chondrocytes are modulated by vitamin D metabolites in a cell maturation-specific manner. 846 52

1. The patch-clamp technique was used to characterize chloride channels from the apical membranes of bovine tracheal epithelial cells. Application of GTP gamma S or NaF to excised patches revealed the existence of a novel type of Cl- channel regulated by G-proteins in a membrane-delimited manner. 2. The channel had a linear current-voltage relationship, with a conductance of 100-120 pS. Its open probability was independent of voltage. 3. The channel was highly anion selective (permeability ratio, PNa/PCl = 0.06 +/- 0.04) and had the halide permeability sequence: I- > Br- > or = Cl- > F-, corresponding to the Eisenman I sequence. This suggested that neither ionic size nor diffusion rate determined ion permeation through the channel. 4. The mole fraction behaviour was studied using fluoride and chloride ions. Mixtures of ions produced currents that would be expected from the linear combination of the two ions acting independently, indicating relatively simple permeation through the pore and compatible with a single ion binding site. 5. The channel was inhibited by the stilbene disulphonates SITS (4-acetamido-4'-isothiocyanatostilbene-2, 2'-disulphonic acid) and DNDS (4,4'-dinitrostilbene-2,2'-sulphonic acid). SITS introduced voltage dependence to channel gating and indicated the possible involvement of lysine residues in the channel permeation pathway. 6. NaF was unable to activate Cl- channels in the presence of the aluminum chelator, deferoxamine mesylate. This indicates that Al3+ ions play an important role in chloride channel activation by fluoride. NaF activation was not dependent on the presence of calcium ions. 7. The channel was insensitive to alkaline phosphatase and to the specific inhibitors of protein phosphatase types I and 2A, okadaic acid and calyculin A. 8. The channels could be activated by GTP gamma S or by NaF in the presence of the phospholipase A2 inhibitor quinacrine, indicating that this enzyme is not involved in channel regulation.
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PMID:Characterization and regulation of a chloride channel from bovine tracheal epithelium. 858 18

Alkaline phosphatase is the marker enzyme for matrix vesicles, extracellular organelles that play a major role in primary bone formation and calcification. Recently, we developed osteosarcoma x fibrosarcoma hybrids in which alkaline phosphatase expression was greatly reduced, a phenomenon known as extinction. In the present study, we used to cell hybrids, LTA-1 and LTA-5, constructed from a human osteoblast-like osteosarcoma. TE85, and a mouse fibrosarcoma, La-t-, to examine the differential distribution of alkaline phosphatase between matrix vesicles and the plasma membrane, postulated to be the parent membrane from which matrix vesicles are derived. While alkaline phosphatase in plasma membranes was extinguished, enzyme activity in matrix vesicles from LTA-1 hybrid cells was 34.2% of that present in matrix vesicles from the TE85 parent cells and 200 times that found in La-t- matrix vesicles. Matrix vesicles from LTA-5 had alkaline phosphatase levels similar to La-t-. When other membrane enzymes (phospholipase A2, 5'-nucleotidase, and Na+/K+ ATPase) were examined, hybrid matrix vesicle and plasma membrane levels were similar to those of TE85 and significantly higher than in La-t- membrane fractions. Northern analysis detected mRNA for alkaline phosphatase in TE85 cells, but not in the hybrids or La-t- cells. In contrast, reverse transcription-polymerase chain reaction (RT-PCR) revealed alkaline phosphatase mRNA in the hybrid cells, but at very low levels. Taken together, the data indicate that regulation of plasma membrane and matrix vesicle alkaline phosphatase is independent and suggest that matrix vesicle biogenesis is independent and distinct from that of plasma membrane biogenesis. Analysis of 1B- and 1L-type alkaline phosphatase mRNA by RT-PCR showed that alternate promoter usage of the alkaline phosphatase gene was not responsible for the differential localization of this enzyme in matrix vesicle. Thus, it is likely that matrix vesicle and plasma membrane alkaline phosphatase are regulated differently at a post-transcriptional level.
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PMID:Osteosarcoma hybrids can preferentially target alkaline phosphatase activity to matrix vesicles: evidence for independent membrane biogenesis. 859 37


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