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)

We have previously shown that osteocalcin synthesis is readily induced by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in MG-63 human osteosarcoma cells (Mahonen et al. (1990) Biochim. Biophys. Acta 1048, 30-37). In the present study, the regulation of osteocalcin synthesis by other hormones of the steroid-thyroid hormone family (retinoic acid, 17 beta-estradiol, triiodothyronine, and dexamethasone) was examined. We found that the other hormones alone had no effects on medium osteocalcin and osteocalcin mRNA concentrations by 96 h of treatment. Compared with 1,25(OH)2D3, however, the combination of 1,25(OH)2D3 with dexamethasone resulted in a greatly reduced medium osteocalcin concentration. Also estradiol and triiodothyronine diminished the stimulatory effect of 1,25(OH)2D3. In contrast, the combination of 1,25(OH)2D3 with retinoic acid resulted in an increased medium osteocalcin concentration. The inhibition of osteocalcin synthesis by dexamethasone and triiodothyronine was accompanied by decreased osteocalcin mRNA levels. Retinoic acid and estradiol, however, did not influence the 1,25(OH)2D3-induced osteocalcin mRNA levels. To examine the specificity of the hormonal effects, the activity of alkaline phosphatase was determined. Both baseline and 1,25(OH)2D3-stimulated alkaline phosphatase activity was found to be inhibited by all other hormones. These results suggest that the steroidal hormones specifically affect osteocalcin synthesis in osteoblastic bone cells, and that complex interactions occur at the level of transcription and/or translation resulting in each case in a finely adjusted rate of osteocalcin synthesis.
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PMID:Modulation of 1,25(OH)2D3-induced osteocalcin synthesis in human osteosarcoma cells by other steroidal hormones. 182 Sep 70

Effects of chlorpromazine on the mineralization and alkaline phosphatase activity (ALP) in the tooth germ were examined and compared with those of retinoic acid and HEBP (1-hydroxyethylidene-1, 1-bisphosphonate). Mandibular first molars from 17-day-old mouse embryos were cultured with or without drugs. Calcium content and ALP in the tooth germ increased gradually from 0 to 7 days in culture, the increase of calcium being preceded by that of ALP. Retinoic acid suppressed increases of calcium and ALP in the tooth germ but not in the specimens precultured for 2 days, suggesting that retinoic acid inhibits the mineralization at an early developmental stage of the tooth. HEBP, a physiochemical inhibitor of mineralization, suppressed the increase of calcium, but significantly enhanced the increased of ALP in the tooth germ. Chlorpromazine, which has an antagonistic action towards calmodulin, also suppressed the increases of calcium and ALP in the tooth germ. Calmodulin antagonists W-7 and W-5 similarly suppressed the increases of calcium and ALP; W-5 had less effects on both calcium and ALP. These results indicate that calmodulin may be involved in the regulation of the mineralization in the tooth germ. These drugs are shown to possess different modes of inhibitory action on the mineralization.
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PMID:[In vitro effect of chlorpromazine on the mineralization of tooth germ in mice--comparison with that of retinoic acid and HEBP]. 190 64

Retinoic acid (RA), the natural acid derivative of vitamin A, can induce the differentiation of some cell lines, such as the murine P19 teratocarcinoma cell line. RA can alter the expression of specific genes and the level of the corresponding protein. This report describes the effect of RA on the level of the alkaline phosphatase (ALP) mRNA and protein in P19 teratocarcinoma cells. RA caused a rapid, dose-dependent, and protein synthesis-dependent induction of ALP activity. The increased enzyme activity was detected 4 h after initiation of treatment and maximum induction of ALP activity required 48 h of RA exposure. Increased enzymatic activity was coincidental with increased levels of both a 67-kDa ALP protein and ALP mRNA. By Northern (RNA) blot analysis the increase of a 2.7-kilobase ALP mRNA was observed within 3 h of RA treatment. The RA-induced enhanced ALP mRNA level did not appear to be mainly due to the stabilization of preexisting mRNA, but rather to an increase in transcription of the ALP gene.
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PMID:Retinoic acid induces the expression of alkaline phosphatase in P19 teratocarcinoma cells. 193 66

We have examined the ability of dexamethasone, retinoic acid, and vitamin D3 to induce osteogenic differentiation in rat marrow stromal cell cultures by measuring the expression of mRNAs associated with the differentiated osteoblast phenotype as well as analyzing collagen secretion and alkaline phosphatase activity. Marrow cells were cultured for 8 days in primary culture and 8 days in secondary culture, with and without 10 nM dexamethasone or 1 microM retinoic acid. Under all conditions, cultures produced high levels of osteonectin mRNA. Cells grown with dexamethasone in both primary and secondary culture contained elevated alkaline phosphatase mRNA and significant amounts of type I collagen and osteopontin mRNA. Addition of 1,25-dihydroxyvitamin D3 to these dexamethasone-treated cultures induced expression of osteocalcin mRNA and increased osteopontin mRNA. The levels of alkaline phosphatase, osteopontin, and osteocalcin mRNAs in Dex/Dex/VitD3 cultures were comparable to those of 1,25-dihydroxyvitamin D3-treated ROS 17/2.8 osteosarcoma cells. Omitting dexamethasone from either primary or secondary culture resulted in significantly less alkaline phosphatase mRNA, little osteopontin mRNA, and no osteocalcin mRNA. Retinoic acid increased alkaline phosphatase activity to a greater extent than did dexamethasone but did not have a parallel effect on the expression of alkaline phosphatase mRNA and induced neither osteopontin or osteocalcin mRNAs. In all conditions, marrow stromal cells synthesized and secreted a mixture of type I and III collagens. However, dexamethasone-treated cells also synthesized an additional collagen type, provisionally identified as type V. The synthesis and secretion of collagens type I and III was decreased by both dexamethasone and retinoic acid. Neither dexamethasone nor retinoic acid induced mRNAs associated with the chondrogenic phenotype. We conclude that dexamethasone, but not retinoic acid, promotes the expression of markers of the osteoblast phenotype in cultures of rat marrow stromal fibroblasts.
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PMID:Dexamethasone induction of osteoblast mRNAs in rat marrow stromal cell cultures. 202 91

Using selective media and complement-mediated lysis of primary cultures of a fetal rat calvarial cell population, we have developed a cell line (OBCK6) that exhibits osteoblastic characteristics. OBCK6 cells demonstrated enhanced parathyroid hormone (PTH)-stimulated adenylate cyclase activity relative to the primary calvarial population, production of alkaline phosphatase activity and type 1 collagen, and the capacity to form mineralized nodules in unsupplemented medium after prolonged (22-26 day) culture. Two sublines, CFK1 and CFK2, which were isolated by dilution cloning, differed morphologically and with respect to growth rate. CFK1 cells demonstrated high PTH and prostaglandin E2-stimulated adenylate cyclase activity, whereas only low PTH-stimulated activity was observed in CFK2 cells. Retinoic acid and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] each reduced PTH-stimulated adenylate cyclase activity in both the cell types. Retinoic acid and dexamethasone reduced and 1,25(OH)2D3 enhanced alkaline phosphatase activity in these cells. PTH significantly augmented alkaline phosphatase activity to a much greater extent in CFK1 than in CFK2 cells. Both CFK1 and CFK2 cells expressed type I but type III collagen, and neither expressed osteocalcin. Strong Alcian blue staining of CFK2 cells was suggestive of a cartilaginous phenotype. These three cell lines, therefore, demonstrated discrete characteristics of skeletal cell function and should provide important models for evaluation of mechanisms of mineralization and for control of skeletal cell growth and mesenchymal differentiation in vitro.
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PMID:Establishment of an osseous cell line from fetal rat calvaria using an immunocytolytic method of cell selection: characterization of the cell line and of derived clones. 224 27

UMR 201 is a nontransformed rat clonal cell line derived from neonatal calvaria with phenotypic characteristics of preosteoblasts. Retinoic acid strongly induces expression of alkaline phosphatase and its mRNA in these cells. Dexamethasone substantially reduced the retinoic acid-induced expression of alkaline phosphatase. This apparent interaction between dexamethasone and retinoic acid effects raised the possibility that interactions may extend to other osteoblast-related phenotypic characteristics in UMR 201 cells. Treatment with dexamethasone resulted in a decrease in the expression of mRNA for pro-alpha 1(I) collagen, but upon coincubation with 1 microM retinoic acid for 24 h, the decrease in mRNA for pro-alpha 1(I) collagen was abrogated. Dexamethasone (Dex) treatment caused a dose-dependent increase in osteonectin mRNA, half maximally effective between 1 nM and 10 nM Dex. One micromolar of retinoic acid alone led to a small increase in expression of osteonectin mRNA but prevented any further increase when Dex was added to retinoic acid-treated cells. To study transcriptional control, osteonectin genomic fragments were linked to the bacterial reporter gene, chloramphenicol acetyltransferase, and introduced by transfection into UMR 201 cells. Dexamethasone increased the transcriptional activity of an osteonectin-chloramphenicol acetyltransferase construct; 100 nM Dex resulted in a 3-fold increase over control cells which was attenuated when 1 microM retinoic acid was added to the incubation, while retinoic acid alone resulted in a 2-fold increase in transcriptional activity. Finally, it was noted that coincubation with retinoic acid and Dex stimulated the proliferation of UMR 201 cells when compared with either treatment alone. This study shows the potential importance of hormonal interactions in the expression of osteoblast function.
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PMID:Opposing influences of glucocorticoid and retinoic acid on transcriptional control in preosteoblasts. 262 42

Retinoic acid has a specific role in cellular differentiation and is believed to act by regulating the transcription of specific genes. In the present work, evidence is provided to show that alkaline phosphatase (ALP) gene expression is mediated by retinoic acid in a model clonal cell line (UMR 201) derived from rat neonatal calvaria. These cells have the characteristics of relatively undifferentiated mesenchymal cells with a very low basal ALP activity which is dramatically increased by retinoic acid. Messenger RNA for ALP was clearly demonstrated when the cells were treated with 1 microM retinoic acid for 24 h. Recombinant human tumour necrosis factor-alpha (recombinant TNF-alpha) interacted with retinoic acid to potentiate the rise in ALP activity, although recombinant TNF-alpha alone had no effect. The potentiation of retinoic acid-induced ALP activity was correlated with an increased amount of mRNA for ALP with the combined treatment. By observing the rate of decay of mRNA for actin and ALP, we were able to demonstrate that the interaction between retinoic acid and recombinant TNF-alpha modulated the steady state of ALP mRNA. The mode of action of recombinant TNF-alpha may serve as a model for other paracrine regulators of cell function.
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PMID:Retinoic acid and tumour necrosis factor-alpha act in concert to control the level of alkaline phosphatase mRNA. 274 44

Retinoic acid (RA) inhibits the increases in alkaline phosphatase (AP) and hormone-stimulated adenylate cyclase that accompany the growth of ROS 17/2.8 osteosarcoma cells in culture. The RA effects were first detected 2 days after initiation of treatment and were dose dependent, with an EC50 of 100 nM. The reduction in the hormone-responsive adenylate cyclase activity was associated with lower levels of beta-catecholamine receptors, without a change in apparent receptor affinity and with lower levels of the GTP-binding proteins Gs and Gi, visualized by NAD-dependent [32P]ADP ribosylation. The reduction in AP was correlated with a decrease in the steady state level of AP mRNA. RA had no effect on cell proliferation or saturation density. Retinoids thus inhibit the same features that are promoted by glucocorticoids in ROS 17/2.8 cells. These features seem to be subject to coordinate regulation, probably at the pretranslational level.
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PMID:Effects of retinoic acid on alkaline phosphatase messenger ribonucleic acid, catecholamine receptors, and G proteins in ROS 17/2.8 cells. 282 98

We have studied the effects of sodium butyrate, retinoic acid, and dimethyl sulfoxide on two human ovarian carcinoma cell lines PE04 and PE01. PE04 cells, after treatment with sodium butyrate at cytostatic doses (2-3 mM for 4 days), exhibited phenotypic changes including induction of alkaline phosphatase and determinants recognized by the monoclonal antibodies 123C3 and 123A8. These effects are not simply the result of cytostasis as they were not produced by dimethyl sulfoxide or retinoic acid. Other markers are also modified by sodium butyrate including lipid, acid mucin, and glycogen. Retinoic acid modulated expression of lipid and CA125, while dimethyl sulfoxide reduced expression of CA125. Other short chain fatty acids such as propionic acid and valeric acid (in addition to butyric acid) also induced alkaline phosphatase and the determinants recognized by 123C3 and 123A8 in PE04 cells. Other differentiation inducers and cytotoxic agents studied did not induce these markers at cytostatic concentrations. The effects of sodium butyrate (and related short chain fatty acids) thus appear to be relatively specific for this cell line.
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PMID:Effect of sodium butyrate and other differentiation inducers on poorly differentiated human ovarian adenocarcinoma cell lines. 316 62

Hidradenitis suppurativa, a chronic relapsing disease of apocrine gland-bearing areas, most frequently occurs in the axillae, groin, perineal, and perianal regions. Hidradenitis of vulva is frequently misdiagnosed and inadequately treated. The case of a 15-year-old nulliparous black female adolescent referred for evaluation of multiple draining fistulas of the anogenital region is presented. Diagnostic studies for granulomatous disease were negative. Results of a barium enema were normal and biopsies were compatible with the diagnosis of hidradenitis suppurativa. She was treated for 22 weeks with isotretinoin, 1 mg/kg daily, with an excellent response. Side effects were minor and included cheilitis, mild xerosis, and a transient elevation of serum alkaline phosphatase levels. Few patients with severe hidradenitis have been responsive to this synthetic vitamin A derivative. A review of the literature indicates that the results of treatment with isotretinoin for hidradenitis have been at best equivocal. Isotretinoin should never be used during pregnancy because of known teratogenic effects. Women of childbearing age must use effective contraception during treatment.
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PMID:Hidradenitis suppurativa of the anogenital region: response to isotretinoin. 342 31


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