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)

The adherence of osteoblast-like cells and the resorption activity of isolated osteoclasts on calcium sulphate hemihydrate (CSH) was investigated. After a 24 h incubation period, alkaline phosphatase staining showed that rat osteoblast-like cells ROS 17/2.8 attached on CSH. Neutral red (NR) and tartrate-resistant acid phosphatase (TRAP) staining revealed that osteoclasts attached on CSH. Furthermore, osteoclasts formed lacunae as revealed by scanning electron microscopy. Although the lacunae formed by osteoclasts on CSH were diverse in shape and form, the most common type had approximately a circular outline, with a well-defined margin similar to those formed on dentine. Less commonly, excavations appeared as a discontinuous area of resorbed CSH with the presence of a circular zone around the non-resorbed area. Finally, by using 10(-9) M calcitonin, evidence was obtained that NR-positive cells were osteoclasts (58.3% and 57.66% decrease of NR-positive mouse and rat cells detected on CSH after 24 h incubation). However, no inhibition was obtained with 10(-11) M calcitonin. The overall number of NR-positive osteoclasts adherent on 256 mm2 CSH was 43 +/- 14 and 42 +/- 3 for mice and rat, respectively. The overall number of TRAP-positive mouse osteoclasts was 67 +/- 12. Acetazolamide (10(-5) M), a carbonic anhydrase inhibitor, inhibited the number of adherent NR osteoclasts on CSH by 50.42% and 41.6% for mouse and rat, respectively. These results indicate that osteoblasts attach on CSH and osteoclasts resorb CSH in vitro.
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PMID:Osteoblast adherence and resorption activity of isolated osteoclasts on calcium sulphate hemihydrate. 857 71

Acute arterial hypertension provokes a rapid decrease in proximal tubule (PT) Na+ reabsorption, increasing flow to the macula densa, the signal for tubuloglomerular feedback. We tested the hypothesis, in rats, that Na+ transport is decreased due to rapid redistribution of apical Na+/H+ exchangers and basolateral Na+ pumps to internal membranes. Arterial pressure was increased 50 mmHg by constricting various arteries. We also tested whether transporter internalization occurred when PT Na+ reabsorption was inhibited with the carbonic anhydrase inhibitor benzolamide. Five minutes after initiating either natriuretic stimuli, cortex was removed, and membranes were fractionated by density gradient centrifugation. Urine output and endogenous lithium clearance increased threefold in response to either stimuli. Acute hypertension provoked a redistribution of apical Na+/H+ exchanger NHE3, alkaline phosphatase, and dipeptidyl peptidase IV to higher density membranes enriched in the intracellular membrane markers. Basolateral membrane Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) activity decreased 50%, 25-30% of the alpha 1-and beta 1-subunits redistributed to higher density membranes, and the remainder is attributed to decreased activity of the transporters. Benzolamide did not alter Na+ transporter activity or distribution, implying that decreasing apical Na+ uptake does not initiate redistribution or inhibition of basolateral Na(+)-K(+)-ATPase. We conclude that PT natriuresis provoked by acute arterial pressure is mediated by both endocytic removal of apical Na+/H+ exchangers and basolateral Na+ pumps as well as decreased total Na+ pump activity.
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PMID:Rapid redistribution and inhibition of renal sodium transporters during acute pressure natriuresis. 876 20

Thiazide diuretics have been shown to decrease bone-loss rate and to improve bone mineral density in patients using this medication. However, the exact role of thiazides on bone cells is still debated. In the present work, we studied whether thiazides could affect the normal features of osteoblasts using the human model cell line MG-63. Hydrochlorothiazide (HCTZ) did not affect cell growth nor DNA synthesis in these cells, yet slightly increased alkaline phosphatase activity in these cells at pharmacologically relevant concentrations. Under similar conditions, HCTZ dose-dependently inhibited 1,25(OH)2D3-induced osteocalcin secretion by these cells (maximal effect, -40 to 50%, P < 0.005). However, HCTZ did not inhibit the basal production of osteocalcin in MG-63 cells (without 1,25(OH)2D3 induction), which was very low to undectable. Two different thiazide derivatives, chlorothiazide and cyclothiazide, and two structurally related sulfonamides with selective inhibition of carbonic anhydrase (Acetazolamide) or hyperglycemic effects (Diazoxide) were also tested. Chlorothiazide (1000 microM) inhibited osteocalcin secretion (-42 +/- 12.7%) at doses 10-fold higher than HCTZ (100 microM) while cyclothiazide was effective at doses of 1 microM (-27 +/- 3.6%), and hence 100-fold lower than HCTZ, compatible with the relative natriuretic effect in vivo of these compounds. Acetazolamide (10 microM) poorly affected osteocalcin secretion at doses 100-fold higher than those needed in vivo to inhibit carbonic anhydrase. Likewise, Diazoxide (100 microM) poorly affected osteocalcin secretion at doses known to promote its biological effect. Higher doses of acetazolamide and diazoxide induced cell death. Neither Acetazolamide nor Diazoxide affected alkaline phosphatase, whereas chlorothiazide had a weak positive effect on this enzymatic activity. The production of macrophage colony-stimulating factor (M-CSF) was stimulated in the presence of 1,25(OH)2D3 (50 nM), TNF-alpha (2 ng/ml) or both in MG-63 cells. HCTZ (25 microM, 24 hr of preincubation) did not modify basal M-CSF production and did not reduce the response to 1,25(OH)2D3 alone. In contrast, HCTZ inhibited the response to TNF-alpha alone (P < 0.05), and also reduced the response to a combination of 1,25(OH)2D3 and TNF-alpha (P < 0.01). In conclusion, these results indicate that thiazide diuretics show a selective inhibition of osteocalcin secretion and M-CSF production by MG-63 cells unlike structurally related drugs. Therefore, these features may explain, in part, the positive effect of thiazides on bone mineral density.
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PMID:Selective effect of thiazides on the human osteoblast-like cell line MG-63. 891 12

Exposure to cadmium (Cd) causes skeletal impairments, such as osteoporosis and osteomalacia, in many mammalian species, including humans. There is, however, some controversy about the mechanism of action of these Cd-induced skeletal effects, although both a direct influence on bone cells and effects that are secondary to renal damage caused by the metal have been demonstrated. In the present study, we cultured calvarial bones from neonatal mice and exposed them to Cd to study the effects of the metal on calcium release and on the activity of some enzymes of importance for bone resorption and bone formation. Cd dose-dependently stimulated calcium release from the bones. Maximal release was noted at Cd concentrations of 0.4-0.8 microM, which was similar to the level of release in the presence of maximal stimulatory concentrations of parathyroid hormone (10 nM) and prostaglandin E2 (10 microM). Cykloheximide (1 microM) inhibited calcium release elicited by Cd, prostaglandin E2 and parathyroid hormone. Cd-induced calcium release was linearly increased from 24 to 72 hr of culture. Production of prostaglandin E2 by the bone specimens was dose-dependently stimulated by Cd and inhibited by 1 microM indomethacin. Cd-induced calcium release was inhibited by acetazolamide (100 microM), indomethacin (1 microM) and ibuprofen (10 microM). Prostaglandin E2-stimulated calcium release was not inhibited by indomethacin. Exposure to 32 microM Cd, present during a 48-hr incubation period, significantly decreased prostaglandin E2-stimulated calcium release from 38.9% to 29.8%. Calcium release induced by parathyroid hormone was more sensitive to inhibition by the metal (i.e., Cd concentrations of 0.2 and 32 microM decreased the release from 37.7% to 31% and 19%, respectively). Cd present in the culture medium during a 48-hr incubation dose-dependently inhibited the activity of alkaline phosphatase and tartrate-resistant acid phosphatase in the bones but did not influence the activity of carbonic anhydrase. We conclude that Cd has a direct stimulatory effect on bone resorption, and this effect is dependent on prostaglandin production and also on protein synthesis. On the other hand, Cd also has an inhibitory effect on bone resorption (i.e., resorption is inhibited by higher concentrations of the metal). Moreover, Cd may impair bone formation by impeding the activity of alkaline phosphatase.
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PMID:Characterisation of the effects of cadmium on the release of calcium and on the activity of some enzymes from neonatal mouse calvaria in culture. 937 63

Parotid and mandibular saliva was obtained from red kangaroos by concurrent acetylcholine isoprenaline stimulation. Salivary proteins were separated by horizontal electrophoresis on either cellulose acetate or starch gels and assessed by specific staining techniques for 23 enzymes commonly found in mammalian tissues and body fluids. Parotid saliva was positive for acid phosphatase, alpha-amylase, carbonic anhydrase, glucose-6-phosphate dehydrogenase, sorbitol dehydrogenase and superoxide dismutase activities. Mandibular saliva was positive for alcohol dehydrogenase in addition to the above six enzymes. The kangaroo salivas lacked activity for alkaline phosphatase, beta-galactosidase and non-specific esterase which occur in saliva from some mammalian species.
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PMID:Enzyme activity in parotid and mandibular saliva from red kangaroos, Macropus rufus. 978 23

Intrinsic chemical properties of the zinc(II) ion in zinc enzymes have been investigated by the model of 1:1 Zn2+-macrocyclic polyamine complexes, including Zn2+-1,5,9-triazacyclododecane ([12]aneN3) and 1,4,7,10-tetraazacyclododecane (cyclen). The physiologically most suitable pKa values for the Zn2+-bound H2O in enzymes were illustrated by the first model Zn2+-[12]aneN3 complex, which mimics the essential kinetic and thermodynamic roles of Zn2+ in carbonic anhydrase. The activation of proximate serine residues (in alkaline phosphatase) and activation of alcohols for hydride transfer to NAD+ (in alcohol dehydrogenase) were also mimicked by Zn2+ -[12]aneN3 complexes. The functions of two zincs in dinuclear metallophosphatases were explained by a new dinuclear Zn2+-cryptate. For an aldolase type II model, a Zn2+-cyclen derivative showed facile enolate formation from a proximate carbonyl pendant under physiological conditions. The strong anion affinities, which Zn2+ intrinsically possesses, were exploited into novel selective nucleobase thymine (or uracil) recognition of Zn2+-cyclen complexes by the strong Zn2+ -imido anion bond formation. The Zn2+-aromatic-pendant cyclen complexes selectively bind to T (or U) in single- and double-stranded DNA (or RNA). Thus, Zn2+ complexes act like molecular zippers to break A-T pairs in DNA, which was proven by various physicochemical measurements and DNA footprinting assays. These Zn2+ complexes showed some relevant biochemical and biological properties such as inhibition of transcriptional factor, TATA binding protein, or strong antimicrobial activities to gram-positive bacterial strains.
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PMID:Why zinc in zinc enzymes? From biological roles to DNA base-selective recognition. 1081 60

This study evaluated the skin adaptation response in Xenopus laevis to short- and medium-term stays (24 h, 48 h, 7 days) in brackish water. Morphological, histochemical, histoenzymological (alkaline phosphatase, carbonic anhydrase) and electrophysiological (short-circuit current, resistance) characteristics were examined. The results show that animals adapt to brackish water, implementing a variety of short and medium-term morphofunctional modifications of the epidermis and skin glands. These modifications form part of the defence mechanisms needed to protect the animal from an excess increase in the saline concentration of internal fluids.
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PMID:Skin morphology and function in Xenopus laevis exposed to a saline environment for up to one week. 1091 71

We recently showed that indapamide (IDP), a thiazide-related diuretic, increases bone mass and decreases bone resorption in spontaneously hypertensive rats supplemented with sodium. In the present study, we evaluated the in vitro effects of this diuretic on bone cells, as well as those of hydrochlorothiazide (HCTZ), the reference thiazide, and acetazolamide (AZ), a carbonic anhydrase (CA) inhibitor. We showed that 10(-4) M IDP and 10(-4) M AZ, as well as 10(-5) M pamidronate (APD), decreased bone resorption in organ cultures and in cocultures of osteoblast-like cells and bone marrow cells in the presence of 10(-8) M 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. We investigated the mechanism of this antiresorptive effect of IDP; IDP decreased osteoclast differentiation as the number of osteoclasts developing in coculture of marrow and osteoblast-like cells was decreased markedly. We then investigated whether IDP affected osteoblast-like cells because these cells are involved in the osteoclast differentiation. Indeed, IDP increased osteoblast-like cell proliferation and alkaline phosphatase (ALP) expression. Nevertheless, it did not modify the colony-stimulating factor 1 (CSF-1) production by these cells. In addition, osteoblast-like cells expressed the Na+/Cl- cotransporter that is necessary for the renal action of thiazide diuretics, but IDP inhibited bone resorption in mice lacking this cotransporter, so the inhibition of bone resorption and osteoclast differentiation did not involve this pathway. Thus, we hypothesized that IDP may act directly on cells of the osteoclast lineage. We observed that resorption pits produced by spleen cells cultured in the presence of soluble osteoclast differentiation factor (sODF) and CSF-1 were decreased by 10(-4) M IDP as well as 10(-5) M APD. In conclusion, in vitro IDP increased osteoblast proliferation and decreased bone resorption at least in part by decreasing osteoclast differentiation via a direct effect on hematopoietic precursors.
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PMID:Indapamide, a thiazide-like diuretic, decreases bone resorption in vitro. 1120 36

In the present study, bone carbonic anhydrase was isolated from ancient human bones and its characteristic features were determined. For this purpose, the skull bone of about 3000 years age was used. The purification was performed in four steps. Four different isoenzymes of CA, including outer peripheral, inner peripheral, integral, and cytosolic were purified and characterized. Affinity chromatography using Sepharose-4B-L-tyrosyn sulfanilamide as a support material was used in its purification. Two different methods were used for enzymatic activity determination: a) hydratase, and b) esterase methods. Bradford and Coomassie Brillant Blue methods were used for protein determination. Optimal pH, temperature, and molecular weight determinations were performed by conventional methods. The purification degree and the subunits, if present, were determined by SDS-PAGE. The effects of some chemicals on the enzyme were also investigated. The most cardinal finding was that the enzymatic activity has been found in antique human bone, showing some other enzymatic activity. That the alkaline phosphatase activity has been determined in the same sample supports the finding of carbonic anhydrase.
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PMID:The activities of carbonic anhydrase and alkaline phosphatase in ancient human bones. Purification and characterization of outer peripheral, cytosolic, inner peripheral, and integral CA. 1151 93

Acute hypertension rapidly inhibits proximal tubule (PT) Na,K-ATPase activity and sodium reabsorption 30 to 40%, increasing sodium and volume delivery to the thick ascending loop of Henle (TALH) and macula densa, providing the error signal for tubuloglomerular feedback. The hypothesis was tested in rats that an acute increase in sodium and volume delivery to the TALH would acutely increase outer medulla Na,K-ATPase activity. Flow to the TALH was increased by either (1) elevating BP (102 to 160 mmHg) for 5 min by constricting arteries (hypertension) or (2) inhibiting PT sodium and volume reabsorption with the carbonic anhydrase inhibitor benzolamide: 2 mg/kg in 300 mM NaHCO(3) at 50 microl/min for 5 to 7 min. Both stimuli increased urine output and lithium clearance three- to four-fold and increased basolateral Na,K-ATPase activity about 40%. In homogenates, acute hypertension increased medullary Na,K-ATPase activity from 20 +/- 3.5 to 27 +/- 6.4 micromol Pi/mg protein per h while decreasing renal cortex activity from 10.9 +/- 0.9 to 6.5 +/- 0.7. Hypertension and benzolamide also doubled medullary alkaline phosphatase activity. As chronic hypertension develops in the young spontaneously hypertensive rat, medullary Na,K-ATPase activity similarly increases. In conclusion, there is a rapid activation of medullary Na,K-ATPase activity during acute hypertension that can be explained by the increase in sodium and volume flow to the region independent of hypertension. That is, the glomerulotubular balance response in the loop of Henle is accompanied by increased Na,K-ATPase activity. The rapid, downstream shift in Na,K-ATPase activity during acute hypertension contributes the driving force for activating TGF (by inhibition in the PT) and minimizes changes in distal sodium delivery (by activation in the TALH).
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PMID:Downstream shift in sodium pump activity along the nephron during acute hypertension. 1167 99


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