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)

We have synthesized several halogenated steroids as potential glucocorticoid receptor mediated imaging agents. These compounds are analogs of aryl-pyrazolo steroids, similar to the potent glucocorticoid, cortivazol. Compounds containing the halogens, iodine, bromine, and fluorine, as well as the E- and Z-iodovinyl side chain at the para position of 2'-phenyl-11 beta,17,21-trihydroxy-16 alpha-methyl-20-oxo-pregn-4-eno[3,2-c] pyrazole were prepared. They were tested as ligands for the glucocorticoid receptor by competition for the binding of [3H]dexamethasone and for glucocorticoid potency by the induction of alkaline phosphatase in HeLa cells. None of the iodinated steroids were good ligands for the glucocorticoid receptor or potent glucocorticoids. The bromo analog was only slightly better than the iodinated steroids as a ligand, and it had a potency in the HeLa cell assay about half that of dexamethasone. The fluoro analog good binding to the glucocorticoid receptor and was a very potent glucocorticoid, approximately seven times that of dexamethasone. Consequently, it appears that the fluoro steroid, 2'-(4-fluorophenyl)-11 beta,17,21-trihydroxy-16 alpha-methyl-20-oxo-pregn-4-eno[3,2-c] pyrazole, when labeled with 18F, would make an excellent glucocorticoid receptor-mediated imaging agent for positron emission tomography.
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PMID:Iodinated and fluorinated steroid 2'-aryl-[3,2-c] pyrazoles as potential glucocorticoid receptor imaging agents. 983 Jun 86

Fluoride has been used for decades, either systemically or topically, to prevent dental caries. The purpose of this study was to clarify the effects of low concentrations of fluoride on proliferation, differentiation and extracellular-matrix synthesis in normal human dental pulp cells (DP-1 and DP-2) in vitro. The effects were compared with those on a human osteoblastic osteosarcoma cell line, TE-85. Fluoride at micromolar concentrations significantly and dose-dependently stimulated [3H]thymidine incorporation into DNA in DP-1, DP-2 and TE-85 cells, with optimal effects around 50 microM, by 127 +/- 7%, 124 +/- 0.6% and 152 +/- 13.4%, respectively. To assess the potential influence of fluoride on cell differentiation, the effects of mitogenic concentrations on alkaline phosphatase activity were measured. Fluoride significantly increased the enzyme's activity in DP-1 and TE-85 by 177 +/- 12% and 144 +/- 12.3%. To evaluate the effect on extracellular-matrix synthesis, the synthesis of type I collagen was indirectly determined by an assay of procollagen type I c-peptide production. Fluoride significantly increased that production by 150 +/- 8.7% in TE-85, but not in either DP-1 or DP-2. These observations suggest that fluoride, if used at low concentrations, could be a useful therapeutic agent where increased regeneration of dentine is desired, such as after pulp amputation, by stimulating the proliferation and differentiation of the dental pulp cells.
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PMID:Stimulation by low concentrations of fluoride of the proliferation and alkaline phosphatase activity of human dental pulp cells in vitro. 1007 54

Fluoride stimulates bone cell proliferation and nodule formation in fetal rat calvarial osteoblastic cells. In addition, fluoride enhances alkaline phosphatase activity, a marker of osteoblastic differentiation, in a dose-dependent manner. The effects of fluoroalumino complex (AlFx) on cell proliferation and differentiation were markedly reduced by tyrosine kinase inhibitor; 1 mM genistein or 1 microg/ml herbimycin. It suggests that tyrosine kinase-mediated mitogenic signaling involves a series of protein-protein interactions between tyrosine-phosphorylated receptors, Shc and Grb2, resulting in an AlFx-induced mitogenic effect. The results indicate that AlFx dose-dependently enhances the tyrosine phosphorylation of the adaptor molecule Shc (p52) and its association with Grb2 in the tyrosine kinase mediated pathway. In addition, AlFx decreases the phosphorylation level of CREB without any change on the amount of CREB protein. Taken together, the results suggest that adaptor proteins, including Shc and Grb2 of the protein tyrosine kinase cascade are implicated in fluoride-induced mitogenic activity of fetal rat calvarial osteoblastic cells. Furthermore, CREB which passes signals from cAMP to transcriptional factor CRE, modulates the fluoroaluminate-induced metabolism of bone cells via a decrease of phosphorylation level.
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PMID:Mechanism of mitogenic effect of fluoride on fetal rat osteoblastic cells: evidence for Shc, Grb2 and P-CREB-dependent pathways. 1095 25

Ammonia oxidation is a rate-limiting step in the biological removal of nitrogen from wastewater. Analysis of microbial communities possessing the amoA gene, which is a small subunit of the gene encoding ammonia monooxygenase, is important for controlling nitrogen removal. In this study, the amoA gene present in Nitrosomonas europaea cells in a pure culture and biofilms in a nitrifying reactor was amplified by in situ PCR. In this procedure, fixed cells were permeabilized with lysozyme and subjected to seminested PCR with a digoxigenin-labeled primer. Then, the amplicon was detected with an alkaline phosphatase-labeled antidigoxigenin antibody and HNPP (2-hydroxy-3-naphthoic acid-2'-phenylanilide phosphate), which was combined with Fast Red TR, and with an Alexa Fluor 488-labeled antidigoxigenin antibody. The amoA gene in the biofilms was detected with an unavoidable nonspecific signal when the former method was used for detection. On the other hand, the amoA gene in the biofilms was detected without a nonspecific signal, and the cells possessing the amoA gene were clearly observed near the surface of the biofilm when Alexa Fluor 488-labeled antidigoxigenin antibody was used for detection. Although functional gene expression was not detected in this study, detection of cells in a biofilm based on their function was demonstrated.
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PMID:Direct detection by in situ PCR of the amoA gene in biofilm resulting from a nitrogen removal process. 1167 54

A two-color fluorescence detection method is described based upon covalently coupling the succinimidyl ester of BODIPY TR-X dye to proteins immobilized on polyvinylidene difluoride membranes, followed by detection of target proteins using the fluorogenic, precipitating substrate ELF 39-phosphate in combination with alkaline phosphatase conjugated reporter molecules. This results in all proteins in the profile being visualized as fluorescent red signal while those detected specifically with the alkaline phosphatase conjugate appear as fluorescent green signal. The dichromatic detection system is broadly compatible with ultraviolet epi- or trans-illuminators combined with photographic or charge-coupled device cameras, and xenon-arc sources equipped with appropriate excitation/emission filters. The dichromatic method permits detection of low nanogram amounts of protein and allows for unambiguous identification of target proteins relative to the entire protein profile on a single electroblot, obviating the need to run replicate gels that would otherwise require visualization of total proteins by silver staining and subsequent alignment with chemiluminescent or colorimetric signals generated on electroblots. Combining the detection approach with an Alexa Fluor 350 dye conjugated monoclonal antibody permits simultaneous fluorescence detection of two antigens and the total protein profile on the same electroblot.
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PMID:Simultaneous red/green dual fluorescence detection on electroblots using BODIPY TR-X succinimidyl ester and ELF 39 phosphate. 1198 24

This paper reports that in the rat coadministration of calcium (calcium chloride, CAS 10043-52-4, Ca2+) enhances intestinal absorption and bioavailability of monofluorophosphate (sodium monofluorophosphate, CAS 10163-15-2, MFP). Evidence obtained with two different experimental models is presented indicating that the latter effects are indirect consequences of the inhibitory effect of Ca2+ on alkaline phosphatase. Pharmacokinetic experiments in previous studies showed that fluorine bound to plasma proteins is the variable that determines the bioavailability of MFP. The area under the curve of fluorine bound to plasma proteins in rats receiving MFP + Ca2+ was significantly greater than in controls. In isolated duodenal loops in situ, Ca2+ increased the intestinal rate constant of MFP absorption and decreased the rate constant of MFP hydrolysis. Inhibition of hydrolysis increased the concentration of MFP at the intestinal lumen. This fact, however, is not only the cause of increased MFP absorption. Inhibition of alkaline phosphatase with L-phenylalanine, to the same extent as with Ca2+, increased MFP absorption with respect to controls but to a lower degree than with Ca2+. The rate constant of MFP hydrolysis by purified rat intestinal alkaline phosphatase was significantly inhibited by 50 mmol/l Ca2+ in comparison to control levels. Ca2+ decreased significantly Vmax of the enzyme (p-nitrophenyl phosphate as substrate) and had no effect on Km value. Lineweaver-Burk plots suggested a noncompetitive inhibition mechanism.
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PMID:Intestinal absorption of disodium monofluorophosphate in the rat as affected by concurrent administration of calcium. 1367 49

Drug interactions are the side effect of administration of two or more drugs or a drug-food combination. Although some drug interactions are intentional and beneficial to the patient, the majority are unintentional and associated with a potentially harmful effect. The aim of this study was to search for interactions in rats between fluoride and zinc administered orally for 12 weeks and to elucidate any potential toxicological and therapeutic consequences. 60 male Wistar rats were divided into six groups of ten rats each and exposed to: 1. controls (distilled water); 2. sodium fluoride (NaF); 3. low-dose zinc (Zn); 4. high-dose zinc; 5. NaF + low-dose Zn; 6. NaF + high-dose Zn. At the end of the experiment the content of F- and Zn+ in serum, urine, incisors, femur and mandible was measured and densitometry of femoral bones was performed. Serum alkaline phosphatase, alanine and aspartate aminotransferase activities, as well as bilirubin and creatinine concentrations were determined to confirm non-toxicity of fluoride dose. Animals receiving NaF only demonstrated higher content of fluorine in serum, urine bones and teeth. Zinc concentrations in serum, urine, bones and teeth were elevated in rats receiving zinc with or without NaF. Fluorine accumulation in bones and teeth was reduced by Zn, but in general the effect lacked statistical significance. Zinc slightly reduced the concentrations of fluorine in serum and urine. Sodium fluoride slightly reduced the concentration of zinc in serum and urine. Bone mineral content (BMC) was significantly increased by NaF and was not further increased by co-administration of zinc. No changes in serum alkaline phosphatase, alanine and aspartate aminotransferase activities, bilirubin and creatinine concentrations were detected. In conclusion, simultaneous administration of fluorine and zinc may be beneficial for prevention and treatment of pathologic conditions in bones and teeth and is not accompanied by an increase in fluorine levels which could be responsible for toxicological symptoms.
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PMID:[Interaction between fluorine and zinc after long-term oral administration into the digestive system of rats]. 1460 70

A double-layered coating, consisting of a hydroxyapatite (HA) outer film and a fluor-hydroxyapatite (FHA) inner film, was produced on a Ti substrate by a sol-gel route to improve the biocompatibility and functionality of the system. Dissolution behavior of and in vitro cellular responses to the layered film were investigated. Calcium nitrate and triethyl phosphite were used for calcium and phosphate precursors, respectively, and ammonium fluoride was added as a fluorine-ion source for FHA. The FHA layer was deposited on Ti by spin coating and subsequent heat treatment at 550 degrees C for 30 min in air, and then the HA layer was laid down over the FHA-coated Ti under the same conditions. After heat treatment, characteristic apatite structures and phases were developed on both FHA and HA films. The cross-section view of the HA/FHA film clearly showed a double-layered structure on Ti with each layer approximately 0.6-0.8-microm thickness. The coating layer was highly uniform and dense, and adhered to Ti substrate strongly with an adhesion strength of about 40 MPa. The in vitro solubility of the HA/FHA layered film in a physiological solution was between that of HA and FHA pure film, and the dissolution profile was quite biphasic, that is, an initial rapid period and a slowdown with increasing time, reflecting the gradient solubility of the fast HA outer structure/slow FHA inner structure. The human osteoblast-like HOS TE85 cells cultured on the HA/FHA layered film attached, spread, and grew favorably. The proliferation rate of the cells on the layered film was significantly higher (considered at p < 0.05 for n = 6) than that on Ti substrate and was similar to that on pure HA film. The alkaline phosphatase (ALP) activity and osteocalcin (OC) produced by the cells on the layered film were significantly higher (considered at p < 0.05 for n = 6) than those on Ti substrate. Moreover, the ALP and OC levels of cells on the layered film showed the trends of HA outer/FHA inner structure with respect to culture period, that is, HA initially and FHA later. These observations suggest that the HA/FHA layered film on Ti obtained by a sol-gel route possesses gradient functionality in terms of solubility and cellular responses, and find that those parameters can be tailored for specific use in hard-tissue implants.
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PMID:Hydroxyapatite and fluor-hydroxyapatite layered film on titanium processed by a sol-gel route for hard-tissue implants. 1536 29

Fluorapatite (FA)-collagen composites were synthesized via a biomimetic coprecipitation method in order to improve the structural stability and cellular responses. Different amounts of ammonium fluoride (NH4F), acting as a fluorine source for FA, were added to the precipitation of the composites. The precipitated composites were freeze-dried and isostatically pressed in a dense body. The added fluorine was incorporated nearly fully into the apatite structure (fluoridation), and a near stoichiometric FA-collagen composite was obtained with complete fluoridation. The freeze-dried composites had a typical biomimetic network, consisting of collagen fibers and precipitates of nano-sized apatite crystals. The human osteoblast-like cells on the FA-collagen composites exhibited significantly higher proliferation and differentiation (according to alkaline phosphatase activity) than those on the hydroxyapatite-collagen composite. These enhanced osteoblastic cell responses were attributed to the fluorine release and the reduced dissolution rate.
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PMID:Stability and cellular responses to fluorapatite-collagen composites. 1560 90

In this report, a series of fluoridated apatite coatings were obtained by the electron-beam deposition method. The fluoridation of the apatite was aimed to improve the stability of the coating and elicit the fluorine effect, which is useful in the dental restoration area. Apatites fluoridated at different levels were used as initial evaporants for the coatings. The as-deposited coatings were amorphous, but after heat treatment at 500 degrees C for 1 h, the coatings crystallized well to an apatite phase without forming any cracks. The adhesion strengths of the as-deposited coatings were about 40 MPa. After heat treatment at 500 degrees C, the strengths of the pure HA and FA coatings decreased to about 20 MPa, however, the partially fluoridated coatings maintained their initial strength. The dissolution rate of the fluoridated coatings was lower than that of the pure HA coating, and the rate was the lowest in the coatings with 25% and 50% fluorine substitutions. The osteoblast-like cells responded to the coatings in a similar manner to the dissolution behavior. The cells on the fluoridated coatings showed a lower (p < 0.05) proliferation level compared to those on the pure HA coating. The alkaline phosphatase activity of the cells was slightly lower than that on the pure HA coating, but this difference was not statistically significant.
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PMID:Fluoridated apatite coatings on titanium obtained by electron-beam deposition. 1562 32


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