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)

When fetal rat calvarial cells are cultured in medium containing vitamin C, osteoid nodules develop after approximately 15 days of culture. Upon addition of an organic phosphate (beta-glycerophosphate, beta GP), these nodules mineralize. We have now used this system to explore the suggestion made by others that a negative feedback may exist between matrix mineralization on the one hand and the synthesis of alkaline phosphatase and bone matrix collagen on the other by analyzing the synthesis of these proteins and the levels of their mRNAs in mineralizing and nonmineralizing cultures. Our results indicate that in the osteoid nodule-bone nodule system, matrix mineralization did not affect the mRNA levels for osteopontin, type I collagen, bone sialoprotein, or osteocalcin. Synthesis of total protein and collagen and the osteocalcin content of culture media were also not different in the mineralizing and nonmineralizing cultures. However, alkaline phosphatase mRNA was increased in early mineralizing cultures and alkaline phosphatase activity in the cell layer was also increased in mineralizing cultures. Thus, the hypothesis that a direct negative feedback exists between mineralization and matrix protein synthesis is not supported by our experiments.
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PMID:beta-Glycerophosphate-induced mineralization of osteoid does not alter expression of extracellular matrix components in fetal rat calvarial cell cultures. 145 88

Osteocalcin is a 49 amino acid non collagenous bone matrix protein which is synthesized by the osteoblasts. The serum levels of osteocalcin have been found to be a specific biochemical parameter of bone formation. We determined the serum levels of osteocalcin, parathyroid hormone, calcitonin and alkaline phosphatase as well as the 2 hour fasting hydroxyproline excretion in 26 patients with postmenopausal osteoporosis and in 24 postmenopausal control subjects. Serum levels of osteocalcin were significantly lower in the patients with postmenopausal osteoporosis than in the control subjects (p less than 0.002). In contrast, serum levels of parathyroid hormone, calcitonin, alkaline phosphatase and the 2 hour hydroxyproline excretion in the patients with postmenopausal osteoporosis and the control subjects were not statistically different. Our data give evidence of a decreased bone formation in patients with postmenopausal osteoporosis.
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PMID:Decreased serum osteocalcin levels in patients with postmenopausal osteoporosis. 179 22

The serum levels of osteocalcin, a 49-amino-acid bone-matrix protein, have been found to be a specific biochemical parameter of bone formation. The aim of our study was to compare the sensitivity of serum osteocalcin levels with that of alkaline phosphatase in the evaluation of patients with primary hyperparathyroidism. In 40 patients with biochemically and histologically confirmed primary hyperparathyroidism, the serum levels of osteocalcin, intact parathyroid hormone, alkaline phosphatase, calcium, phosphorus, and creatinine were determined preoperatively. The serum levels of osteocalcin were elevated in 22 patients (55%), whereas the serum levels of alkaline phosphatase were increased in 18 patients (45%). In 10 patients (25%) the serum levels of osteocalcin, but not those of alkaline phosphatase, were increased, whereas in six patients the activity of alkaline phosphatase was high, but the serum osteocalcin levels were normal. When the biochemical data of the patients with increased serum osteocalcin levels were compared with those of the patients with serum osteocalcin levels within the normal range, the serum levels of intact parathyroid hormone and alkaline phosphatase were significantly increased in the group of patients with elevated serum osteocalcin levels. Our data indicate that serum osteocalcin levels might be a clinically useful additional parameter in the evaluation of patients with primary hyperparathyroidism.
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PMID:Serum osteocalcin levels in primary hyperparathyroidism. 188 98

Human osteoblasts derived from long bone periosteum were induced to mineralize in culture in the presence of 2 mM alpha-glycerophosphate, with typical characteristics of mineralization, namely, accumulation of hydroxyapatite and increases in alkaline phosphatase activity and in osteocalcin production. Mineralization was also enhanced by 10(-8) M 1 alpha, 25-dihydroxyvitamin D3. In this system, a prostaglandin A1 derivative, TEI-3313, with the chemical structure 5-[(Z,2E)-4,7-dihydroxy-2-heptenyridene]-4-hydroxy-2-methylthio-4- (4- phenoxybutyl)-2-cyclopentenone, was found to enhance mineralization as effectively as 1 alpha, 25-dihydroxyvitamin D3, although its potency was 10 times lower than that of the vitamin D3 metabolite. Osteocalcin, a bone-specific noncollagenous matrix protein, accumulated onto the cell layers by treatment with TEI-3313 to a much greater extent than those released into the culture medium. TEI-3313 also enhanced collagen synthesis. Based on the finding that TEI-3313 enhanced the synthesis of both collagen and noncollagenous protein, it is speculated that TEI-3313 enhanced the mineralization by stimulating the expression of various genes in osteoblasts.
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PMID:Enhancement of in vitro mineralization in human osteoblasts by a novel prostaglandin A1 derivative TEI-3313. 189 Jun 16

Serum levels of osteocalcin, a noncollagenous bone matrix protein, have been found to be a specific biochemical parameter of bone formation. In the literature in subjects with osteoporosis, an increased incidence of lactase deficiency has been described. We therefore determined the serum levels of osteocalcin in 10 patients with lactase deficiency and in 20 control subjects by radioimmunoassay. The patients with lactase deficiency were dietary treated and had a very low daily calcium intake. Serum osteocalcin levels were significantly higher in the patients with lactase deficiency than in the control subjects. In contrast, serum levels of parathyroid hormone, alkaline phosphatase, calcium, and phosphorus were not statistically different in the two groups. Our data suggest an increased rate of bone turnover in patients with lactase deficiency on a low calcium diet; possibly calcium supplementation is indicated in dietary-treated patients with lactase deficiency.
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PMID:Increased serum osteocalcin levels in patients with lactase deficiency. 189 34

The reversibility of hepatic fibrosis was investigated in an experimental model of extrahepatic cholestasis in the rat after common bile duct ligation for 2 weeks, followed by bilioduodenal anastomosis for 3 weeks. Bile duct ligation resulted in a transitory marked elevation in the serum concentration of 5'-nucleotidase, alkaline phosphatase, and bilirubin during the first 3 days. Then these levels decreased to threefold, twofold, and 100-fold the normal values, respectively, during the following 4 weeks. Histologic examination of the liver disclosed extensive bile duct proliferation and the formation of periportal fibrosis, with only slight inflammation and necrosis. The distribution of the major components of the hepatic extracellular matrix was analyzed 2 weeks after bile duct ligation, using the indirect immunoperoxidase method. Fibrous septa were found to be strongly stained for collagens I, pro-III, III and IV, fibronectin, and laminin. The most intense staining was found in enlarged periportal areas, collagen IV and laminin being particularly abundant around newly formed bile ducts. These changes paralleled high steady-state levels of alpha 1(I) and alpha 1(IV) collagen and B2 chain laminin mRNAs. Relief of the obstruction for 2 weeks resulted in a shift in the serum concentration of 5'-nucleotidase, alkaline phosphatase, and bilirubin toward normal values. A dramatic resorption of bile duct proliferations and periportal fibrosis were observed. Three weeks after bile duct repermeabilization, immunohistochemical study showed that the pattern of distribution of extracellular matrix components was almost normal, except for collagen IV, which remained abundant in the sinusoids when compared with the normal liver. In parallel, the steady-state B2-chain laminin mRNA level became lower than in cholestatic livers, whereas alpha 1(I) and alpha 1(IV) mRNAs were almost undetectable. These results show that hepatic fibrosis induced by experimental extrahepatic cholestasis in rat disappears in less than 3 weeks after relief of bile duct obstruction, suggesting that an active degradation of matrix protein occurs, except for collagen IV in the sinusoid.
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PMID:Reversibility of hepatic fibrosis in experimentally induced cholestasis in rat. 226 Jun 23

Estrogen is important for both the sexual dimorphism of the skeleton during growth and the maintenance of bone balance in adults. This report describes the in vivo effects of estrogen on bone formation and gene expression in the tibial diaphysis of ovariectomized rats. Rats were ovariectomized at 8 weeks of age and were given diethylstilbestrol (DES) or placebo 1 week later as sc sustained release pellets. Histomorphometry revealed that that the periosteal bone formation and apposition rates were reduced at the tibial diaphysis 1 week after beginning estrogen treatment and further reduced after 2 weeks. Interestingly, DES treatment had no effect on endosteal bone formation, but suppressed endosteal bone resorption. Northern analysis of freshly isolated periosteal cells from tibiae and femora revealed that DES treatment resulted in dramatic decreases in steady state mRNA levels for the bone matrix proteins osteocalcin, prepro alpha 2(I) chain of type 1 collagen, osteonectin, and osteopontin as well as the osteoblast marker enzyme alkaline phosphatase. The results suggest that the inhibitory effects of estrogen on radial bone growth in rats are mediated, or at least accompanied, by the inhibition of the expression of bone matrix protein genes in periosteal cells.
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PMID:Estrogen inhibition of periosteal bone formation in rat long bones: down-regulation of gene expression for bone matrix proteins. 238 57

Two new bone cell lines were established by immortalizing cells derived from embryonic rat calvariae with a recombinant retrovirus containing the cDNA for SV-40 large T antigen and the neomycin resistance gene. One cell line, RCT-1, isolated from early digest cells, a population which typically does not express osteoblastic features, displayed osteoblastic characteristics only after 3 days of treatment with 1 microM retinoic acid: alkaline phosphatase activity increased from 0.003 to 0.25 mumol/min.mg protein, the steady state level of type I procollagen mRNA increased 4-fold, and the cells acquired a PTH-stimulatable adenylate cyclase (EC50, 10 nM). mRNA for osteopontin, an abundant bone matrix protein, was induced in RCT-1 cells by 1,25-dihydroxyvitamin D3 (10 nM). The second cell line, RCT-3, isolated from late digest cells, a population previously shown to be enriched with differentiated osteoblasts, expressed constitutively the properties described above. In addition, RCT-3 cells responded to interleukin-1 by increased prostaglandin production (EC50, 20 pM) and to prostaglandin E2 by enhanced cAMP accumulation, features exhibited by calvarial cells in organ culture. Thus, the SV-40 immortalized cell lines we describe retained many of the characteristics of osteoblasts in primary culture, including hormonal regulation of phenotype-related genes. In RCT-1 cells the coordinate induction of several properties by retinoic acid offers a new model for the study of differentiation-related gene expression in bone cells.
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PMID:Rat calvarial cell lines immortalized with SV-40 large T antigen: constitutive and retinoic acid-inducible expression of osteoblastic features. 247 May 84

The mechanism of determination of early embryonic cells has been investigated using sea urchin embryos. An efficacious method of isolating blastomere pairs from the animal or vegetal half of sea urchin embryos was developed. The overt differentiation of separated animal and vegetal blastomere pairs resembles that of separated animal and vegetal hemispheres isolated by manual dissection. Treatment of animal blastomeres with LiCl caused them to display a morphology resembling that of isolated vegetal blastomeres. The effects of separation of animal and vegetal blastomeres and of treatment of animal blastomeres with LiCl were examined at the molecular level using gut alkaline phosphatase and a spicule matrix protein RNA as markers of differentiation. Histochemical staining and in situ hybridization studies showed that these markers are normally only expressed in vegetal blastomeres but that their expression can be evoked in animal blastomeres by treatment with LiCl.
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PMID:Lithium evokes expression of vegetal-specific molecules in the animal blastomeres of sea urchin embryos. 272 45

Osteocalcin (OC), also called Bone Gla Protein (BGP), is a bone matrix protein of 5800 MW synthesized by osteoblasts. Since OC is mainly metabolized in the kidney, its blood concentration is altered in renal failure. The relationship between OC and the calcium-phosphorus regulating hormones (parathyroid hormone, calcitonin) and the biochemical parameters of bone metabolism (serum calcium, serum phosphorus and serum alkaline phosphatase) was studied in 30 patients on chronic hemodialysis (mean age: 51 years; mean duration of dialysis treatment: 39 months). OC levels were significantly elevated in all patients on chronic hemodialysis (34.7 +/- 31.5 ng/ml) when compared to healthy subjects (6.25 +/- 1.39 ng/ml, p less than 0.001). In 2 patients the OC levels were excessively high (127.54 ng/ml; 148.02 ng/ml), which was associated with severe renal osteodystrophy due to secondary hyperparathyroidism. When divided into 2 groups in the patients with secondary hyperparathyroidism the mean OC value was markedly elevated (50.5 +/- 12.7 ng/ml) compared to the patients without secondary hyperparathyroidism (24.1 +/- 2.8 ng/ml) (p less than 0.05). 70 per cent of the patients on chronic hemodialysis with OC levels greater than 30 ng/ml showed moderate to severe scintigraphic findings of bone disease. In neither of the 2 groups could a correlation between OC and serum alkaline phosphatase be demonstrated. The results indicate, that OC levels could be useful additional parameter in hemodialyzed patients with secondary hyperparathyroidism and OC levels could reflect bone formation in these patients.
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PMID:[Osteocalcin in chronic hemodialysis patients as an additional parameter in the diagnosis of advanced secondary hyperparathyroidism]. 278 25


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