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)

A mutual antagonism exists between interleukin-1s (IL-1s) as pro-inflammatory and glucocorticoids as anti-inflammatory mediators. This report examines the effects of IL-1 on the induction by dexamethasone of alkaline phosphatase in LEII murine endothelial cells. Dexamethasone increases the specific activity of alkaline phosphatase in a time- and dose-dependent fashion (maximum 14-fold induction at 10(-6) M, IC50 = 10(-8) M), and this induction can be completely inhibited by simultaneous incubation with picomolar concentrations of recombinant human IL-1 alpha or IL-1 beta. This IL-1-mediated antagonism of dexamethasone activity is not due to a down-regulation of glucocorticoid receptors in the cell line used, because the number of receptors and their affinity for dexamethasone is unchanged in IL-1-treated cells. However, induction of alkaline phosphatase by dexamethasone in LEII cells is receptor-mediated, since it can also be inhibited by glucocorticoid-receptor antagonists.
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PMID:Recombinant human interleukin-1 inhibits the induction by dexamethasone of alkaline phosphatase activity in murine capillary endothelial cells. 350 Sep 55

Dexamethasone is an important regulator of cellular proliferation and differentiation, but paradoxical effects have been noted in a variety of culture systems. The purpose of this study was to determine whether dexamethasone induces proliferation and differentiation of osteogenic precursor cells. Periosteal explants from embryonic chicks were grown in culture for 3 or 4 days, treated continuously with dexamethasone or ethanol vehicle, and then either pulse-labeled with 3H-thymidine at 3 days or labeled for 24 hr between day 3 and day 4. Histochemical and autoradiographic procedures were used to assess the proliferation and differentiation of osteogenic cells. At 3 days, the area of bone, the percentage of alkaline phosphatase-positive cells, the percentage of 3H-thymidine-labeled cells, and the percentage of cells labeled with both markers were significantly higher in dexamethasone-treated cultures. Between day 3 and day 4 no significant changes in these parameters were observed in the dexamethasone-treated cultures. In comparison, control cultures exhibited significant increases in the percentage of 3H-thymidine-labeled cells after 24 hr of continuous labeling. The data show that dexamethasone induces a burst of proliferation in a cohort of cells that undergo differentiation. Once these cells have divided, further proliferation within the culture is limited. Finally, it is apparent that the timing of experiments may be critical in determining whether dexamethasone will inhibit or stimulate proliferation.
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PMID:Dexamethasone induces proliferation and terminal differentiation of osteogenic cells in tissue culture. 374 Apr 74

Dexamethasone increased alkaline phosphatase levels up to 7-fold in the osteoblast-like rat osteosarcoma cell line ROS 17/2.8. This effect was associated with reduced cell growth and took place over several days in culture. The increase in enzyme activity was dose dependent, (half-maximum near 1 nM, with a hormone specificity suggesting glucocorticoid receptor mediation). Dexamethasone also increased enzyme activity in ROS 2/3 cells, but not in two nonosteoblastic osteosarcoma cell lines, indicating that among these cell lines, the effect is specific for osteoblast-like cells. Moreover, enzyme activity in both control and dexamethasone-treated cells correlated directly with levels of radioimmunoassayable bone-type isoenzyme. Increases in alkaline phosphatase activity in response to dexamethasone were detectable after about 5 h and were inhibited by both actinomycin D and cycloheximide. Thus glucocorticoids appear to increase de novo enzyme synthesis in ROS 17/2.8 cells. Finally, the cAMP-elevating agents PTH, isoproterenol, and 8-bromo-cAMP, which were previously shown to reduce alkaline phosphatase activity in osteoblast-like cells, antagonized the effects of dexamethasone. Moreover, in the presence of dexamethasone, lower concentrations of these agents were required for inhibitory effects on alkaline phosphatase.
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PMID:Glucocorticoid regulation of alkaline phosphatase in the osteoblastic osteosarcoma cell line ROS 17/2.8. 385 55

Several enzymes associated with the hepatocyte cell surface, alkaline phosphatase (AP), 5'-nucleotidase (5'N), Mg++- and total Na+K+Mg++-ATpase, were assayed and localized cytochemically in order to gain insight into alterations of the plasma membrane components during reassociation of hepatocytes in primary monolayer culture. During a period of 4 days the activities of 5'nucleotidase and alkaline phosphatase increased spontaneously up to three- and four-fold, respectively. Dexamethasone reinforce the rise of alkaline phosphatase activity but retarded the increase of that of 5'nucleotidase. However, after the third day the level of 5'nucleotidase activity converged with the untreated controls. The activities of Mg++- and Na+K+Mg++-ATPase, which closely paralleled each other, remained essentially unchanged throughout cultivation and were not affected by dexamethasone. Cytochemical demonstration of alkaline phosphatase, 5'nucleotidase and Mg++-ATPase, using the lead salt method, revealed the potential presence of reaction product on the whole cell surface. However, the cells did not react uniformly, particularly on bile canalicular membranes. This heterogeneity seems to be due to different stages of canalicular development and to different functional states of the cultured hepatocytes.
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PMID:Alterations in activity and ultrastructural localization of several phosphatases on the surface of adult rat hepatocytes in primary monolayer culture. 612 58

Effects of corticosteroids and surgical stress on hepatic morphologic features and enzymes were studied in 18 mature dogs of mixed breeding: group 1, control (n = 3); group 2, dexamethasone (n = 5); group 3, dexamethasone and surgery (n = 5); and group 4, surgery (n = 5). Dexamethasone (2.2 mg/kg of body weight twice a day subcutaneously) was administered for 8 days in groups 2 and 3 dogs. All dogs were anesthetized with thiopental for 10 minutes on days 0, 2, and 4. On day 2, dogs in groups 3 and 4 were intubated and maintained on methoxyflurane and oxygen, and a liver biopsy, hemilaminectomy (T13-L1), and 15 minutes of hypotension (75/45 mm of Hg) induced by methoxyflurane were done. Serum alkaline phosphatase (ALP) activity, ALP isoenzymes, and alanine aminotransferase (ALT) activity were determined on days 0, 2, 3, 5, and 8. All dogs were euthanatized and necropsied on day 8. Serum hepatic enzyme activity and hepatic morphologic characteristics were normal for group 1 control dogs. The mean ALP and ALT were significantly (P less than 0.05) increased in dogs in groups 2, 3, and 4. In group 2, the mean ALP (days 5 to 8) and ALT (day 8) were significantly (P less than 0.05) increased. In group 3, the mean ALP and ALT activities were significantly increased on days 2 to 8. In group 4, the mean ALP was significantly increased on days 2 to 8 and the mean ALT was significantly increased on days 3 and 5. All other values were normal. A single isoenzyme band (Rf = 0.399 +/- 0.023, mean +/- SD) was identified in all dogs. Hepatic morphologic changes attributed to dexamethasone were mild-to-moderate vacuolation in a diffuse distribution on day 2 (group 3) and aggregates of moderate-to-severe vacuolation in mainly a periportal distribution on day 8 (groups 2 and 3).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of dexamethasone and surgical hypotension on hepatic morphologic features and enzymes of dogs. 665 Sep 53

Jejunal mucosa of 6 d-old rats were cultured for 24 and 48 h in the presence of thyroxine, insulin, pentagastrin, glucagon, epidermal growth factor (EGF) or dibutyryl-A-3:5-MP cyclic with or without dexamethasone (DX). The enzymes were assayed on the purified brush borders. The various agents added alone to the basic culture medium had no effect with the exception of DX on the levels of enzyme activities. Dexamethasone alone induced sucrase, stimulated maltase, and protected other brush border enzyme activities (aminopeptidase, lactase, and alkaline phosphatase). When added to DX-supplemented medium, only the following factors modified the levels of enzymatic activities observed with DX alone. Insulin (10(-6) M) increased maltase, alkaline phosphatase, and lactase activity to a greater extent than DX at 24 h culture, the effect being maintained at 48 h on alkaline phosphatase only. At 48 h culture, both EGF (10(-8) M) and dbcAMP (10(-3) M) decreased DX-induced sucrase activity. The latter agent also depressed DX-stimulated aminopeptidase activity.
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PMID:Organ culture of suckling rat intestine: comparative study of various hormones on brush border enzymes. 674 50

The effects of glucocorticoids on hormone secretion by human placenta in organ culture were studied. The addition of cortisol resulted in a fourfold increase in human chorionic gonadotropin (hCG) secretion over that in untreated cultures after 144 hours' incubation (P less than 0.05), and a twofold increase in hCG was observed in the presence of cortisone (P less than 0.01). Dexamethasone stimulated hCG secretion in a dose-response manner (r = 0.9542; P less than 0.01). Progesterone, which suppresses hCG under these conditions, decreased the cortisol-enhanced secretion of hCG (r = -0.9794; P less than 0.01). No change in the secretion of human chorionic somatomammotropin was observed, but glucocorticoids increased heat-stable alkaline phosphatase activity (P less than 0.001). The physiologic significance of glucocorticoid effects on placental hormone synthesis is discussed.
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PMID:Stimulation of human chorionic gonadotropin secretion by glucocorticoids. 706 25

Application of dexamethasone was found to induce an enhanced expression level of mRNA encoding the growth associated protein (GAP-43) after peripheral nerve injury. Following hypoglossal nerve axotomy, a dexamethasone releasing pellet (1.5 mg released in 3 weeks) was placed near the transected nerve. GAP-43 mRNA was detected in the hypoglossal nucleus by non-radioactive in situ hybridization histochemistry using an alkaline phosphatase-labeled oligonucleotide probe. A significant elevation of GAP-43 mRNA level was observed 2 weeks after the transection in dexamethasone treated animals. This induction was not observed in the dorsal motor nucleus of vagus which expresses moderately high levels of GAP-43 mRNA even without nerve injury. Although dexamethasone did not alter the maximum level of GAP-43 mRNA in the hypoglossal nucleus after nerve injury, it prolonged the period in which the mRNA expression remained elevated. This may be due to post-transcriptional effect by the glucocorticoid. Dexamethasone treatment also caused a slight facilitation of reprojection. This may be due to the enhancement of GAP-43 mRNA level by the glucocorticoid.
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PMID:Dexamethasone enhances level of GAP-43 mRNA after nerve injury and facilitates re-projection of the hypoglossal nerve. 750 Aug 42

Bone marrow stromal cells comprise a heterogeneous population including fibroblastic, adipocytic, hemopoietic, and osteogenic cells. Although the conditions under which different lineages are regulated have not been fully elucidated, dexamethasone clearly stimulates osteogenic expression in stromal cultures. The purpose of this study was to begin to elucidate and quantify some of the subpopulations present when rat bone marrow stromal cells are grown with or without dexamethasone under conditions favoring bone formation. Bone marrow stromal cells from young adult rats were cultured with ascorbic acid, beta-glycerophosphate, and with or without dexamethasone for various periods of time. Culture dishes were then analyzed for cell counts, or stained with either histochemical or immunohistochemical stains, and colony types were quantitated, or cells were processed for flow cytometry. Dexamethasone significantly increased the number of alkaline phosphatase (AP) positive colonies, von Kossa positive bone nodules, alpha-naphthylbutyrate esterase positive colonies, and ED2 positive (macrophage) colonies. The number of adipocytic foci was largely unaffected in these experiments. Flow cytometry confirmed colony counts and showed stimulation by dexamethasone of AP positive cells and macrophages, and in addition, the reduction of hemopoietic cells expressing leukocyte common antigen. These data show conclusively that when rat bone marrow stromal populations are grown under conditions stimulating osteoprogenitor differentiation and bone formation, the stromal subpopulation make-up, including expression of hemopoietic lineages, is markedly altered.
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PMID:Dexamethasone alters the subpopulation make-up of rat bone marrow stromal cell cultures. 775 9

To facilitate the study of regulators of differentiation and proliferation of small intestinal epithelium in the suckling rat we have developed a serum-free organ culture system and used it to examine epithelial responsiveness to various regulatory hormones. These hormones included the insulin-like growth factors (IGFs) whose action can be blocked by binding proteins in serum. Jejunal explants from 5-day-old suckling rats maintained better brush border enzyme activity and better histology when cultured under hyperbaric conditions for 24 h in serum-free Dulbecco's modified Eagle's medium/F12 medium than in RPMI 1640 plus 10% fetal bovine serum. Tissue responsiveness to various regulatory hormones was then tested in the serum-free medium. Insulin had no significant effect on morphology, proliferation rate, or enzyme activity in 5-day explants after 24 h in culture. However, insulin did increase lactase activity and induce the early appearance of sucrase in 10- and 12-day explants after 48 h in culture. Dexamethasone increased specific activities of alkaline phosphatase (30%, P < 0.001) and lactase (15%, P < 0.001), and reduced shedding of alkaline phosphatase into the medium (P < 0.001), in explants of 5-day-old rats cultured over 24 h. Dexamethasone combined with insulin had no obvious effect on the rate of protein or DNA synthesis but did increase villus height (P = 0.04) and crypt depth (P = 0.001) and acted synergistically to further increase lactase activity above levels obtained by either alone. IGF-I and IGF-II, des-(1-3)IGF-I, fibroblast growth factor (FGF), and growth hormone (GH) had no effect on morphology or biochemical activity of explants after 24 or 48 h culture.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serum-free organ culture of suckling rat jejunum: effect of regulatory hormones. 795 13


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