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)

Biochemical evidence for hypoparathyroidism and roentgenographic evidence for hyperparathyroidism were present in a 7-year-old girl with seizures and tetany. She was hypocalcemic (4.7 mg/dl), hyperphosphatemic (11 mg/dl), and normomagnesemic, with elevated parathyroid hormone level (2,603 pg/dl and 3,693 pg/dl in immunoassays utilizing two different antisera). Somatic features of pseudohypoparathyroidism were absent. Increased serum alkaline phosphatase activity (335 IU/liter) with evidence of subperiosteal bone resorption suggested parathyroid hormone activity on bone. Intramuscular administration of parathyroid extract caused a rise in serum calcium level (9.6 mg/dl) and a fall in serum phosphorus level (7.9 mg/dl). The serum calcium, phosphorus, and alkaline phosphatase activity became normal during vitamin D therapy. Parathyroid hormone values and bone roentgenograms became normal. With serum calcium and phosphorus levels normal, ethylenediaminetetraacetic acid infusion was followed by an increase in plasma parathyroid hormone level but not in urinary cyclic adenosine monophosphate (AMP) or phosphaturia; in contrast, parathyroid extract induced cyclic AMP excretion and phosphaturia. These results suggest that endogenous parathyroid hormone in this patient affects bone resorption but not renal handling of phosphate. We infer that this represents a defective endogenous parathyroid hormone.
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PMID:Hypo-hyperparathyroidism: evidence for a defective parathyroid hormone. 19 77

Parathyroid hormone degradation is intimately connected with its action. By the action of the unique renal neutral cytosolic PTH ase, PTH is split into 1-34 and 35-84 fragments, and further into 35-70 and 71-84 fragments. Amino-terminal 1-34 peptide was found to participate in the autoregulation of PTH secretion, suppressing the intact PTH secretion both in vivo in humans and in vitro in the dispersed bovine parathyroid cells. C-terminal fragment 35-84 and N-terminal fragment 1-34 both suppress the alkaline phosphatase production by ROS 17/2.8 cells to a lesser extent than the intact PTH 1-84, and the sum of the effects of the two fragments approximately equaled that of the intact hormone. Fragments 35-70 and 71-84 were devoid of such activity. Intracellular free calcium of human vascular endothelial cells was raised by intact 1-84, lowered on the contrary by C-terminal 35-84 fragment, but fragments 1-34, 35-70 and 71-84 had no effect. Fragments generated by the actions, supporting the physiological significance of PTH degradation by its target cells.
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PMID:New actions of parathyroid hormone through its degradation. 130 Mar 29

Parathyroid hormone (PTH), osteocalcin and alkaline phosphatase (AP) were investigated before and after parathyroidectomy in 12 patients receiving hemodialysis. Early post-parathyroidectomy, PTH decreased (p less than 0.001), AP increased (p less than 0.05), but osteocalcin remained unchanged. At 3 months, osteocalcin and AP declined. A negative correlation was observed between aluminum staining and post-parathyroidectomy osteocalcin. In conclusion, early post-parathyroidectomy, osteocalcin and AP reflect persistent osteoblastic activity, which declined after 3 months. In patients receiving hemodialysis both variables may represent different aspects of osteoblastic activity and osteocalcin allows mixed uremic osteodystrophy after parathyroidectomy.
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PMID:Evolution of osteocalcin, alkaline phosphatase and parathyroid hormone after parathyroidectomy in patients receiving chronic maintenance hemodialysis. 157 55

The effects of factors known to influence bone metabolism were examined using the osseous cell line CFK1. Parathyroid hormone (PTH) and dexamethasone (DEX) appeared to enhance the formation of cell foci of CFK1 cells in culture whereas retinoic acid (RA) caused a marked alteration in individual cell morphology. Bone morphogenetic protein (BMP-2) and PTH increased alkaline phosphatase activity, however, this index of differentiation was suppressed by epidermal growth factor (EGF), DEX, and RA. BMP-2 and EGF each stimulated DNA synthesis in a dose-dependent manner and enhanced cell numbers, but, no synergistic response of EGF and BMP-2 was observed. PTH and DEX failed to significantly alter cell number or EGF-stimulated DNA synthesis or cell proliferation. Although RA treatment of CFK1 cells resulted in a reduction in cell number compared to control, pretreatment with RA enhanced EGF-stimulated DNA synthesis and proliferative effects. At least part of this effect was by increasing the EGF receptor binding capacity of the cells. Furthermore, using cell cycle analysis, addition of EGF stimulated the progression of RA-treated cells into the DNA synthesis (S) phase with a reduced lag time. EGF and BMP-2, therefore, appear to exert a role in the expansion dynamics of the CFK1 population although BMP-2 may also enhance differentiation. PTH and DEX may act primarily to modulate the differentiated function of the CFK1 cells. RA inhibited cell proliferation and may mediate differentiation towards a less established cell population with upregulation of EGF receptors. The CFK1 cell model may, therefore, provide insight into microenvironmental control of growth and differentiation of precursor osseous cells.
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PMID:Effect of protein and steroidal osteotropic agents on differentiation and epidermal growth factor-mediated growth of the CFK1 osseous cell line. 163 66

Experiments have been carried out to determine the mechanisms involved in the formation of osteoclast-like cells from spleen cells in mice. Osteoclasts were defined as tartrate-resistant acid phosphatase-positive multinucleated cells (TRACP-positive MNCs) in which specific calcitonin receptors were identified by autoradiography with labeled salmon calcitonin. Furthermore, cultures rich in these cells produced resorption pits when grown on dentine slices. Several clonal cell lines were obtained from fetal mouse calvariae and screened for their ability to induce TRACP-positive MNCs in response to 1 alpha, 25-dihydroxyvitamin D3 [1 alpha, 25(OH)2D3] in co-cultures with spleen cells. A cell line, KS-4, was identified with the greatest potency in inducing osteoclast-like cell formation in co-culture with spleen cells. The capacity of KS-4 cells to produce this effect was much greater than that of two bone marrow-derived stromal cell lines (MC3T3-G2/PA6 and ST2 cells), which we have previously shown to be effective in this system but to require treatment with dexamethasone in addition to 1 alpha, 25(OH)2D3 (Udagawa et al.: Endocrinology 125:1805-1813, 1989). Parathyroid hormone (PTH) increased cAMP production in KS-4 cells, and PTH and interleukin-1 alpha also induced TRACP-positive MNCs in co-cultures with spleen cells. Contact between living KS-4 and spleen cells was necessary for osteoclast formation to take place, since this did not occur when the two populations were separated by a membrane filter, or when the KS-4 cells were killed by fixation. Separate cultures of either spleen cells or KS-4 cells formed no TRACP-positive MNCs. KS-4 cells synthesized predominantly type I collagen, formed bone nodules without added of beta-glycerophosphate in a long-term culture, and expressed increasing alkaline phosphatase activity after confluence in culture. These results indicate that the KS-4 cells have properties consistent with progression toward the osteoblast phenotype and represent a single cell line with the ability to promote osteoclast formation by a contact-requiring process.
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PMID:Cloning of an osteoblastic cell line involved in the formation of osteoclast-like cells. 170 73

Eleven Nigerian children with clinically and radiologically proven rickets were assessed biochemically. The children had low or low normal concentrations of total and corrected calcium, and elevated plasma alkaline phosphatase (ALP) activity, but normal plasma phosphate concentrations. Their serum 25-hydroxyvitamin D (25-OHD) and 1,25-dihydroxyvitamin D (1,25-(OH)2D) concentrations were not significantly different from those in controls, but the ratio of 1,25-(OH)2D to 25-OHD was significantly greater than that in controls. Parathyroid hormone (PTH) concentrations were greater in rachitic children, and there was a significant correlation between 1,25-(OH)2D and PTH concentrations. Osteocalcin concentrations in rachitic children were not significantly different from those in controls, but they were markedly elevated in the three patients with the highest 1,25-(OH)2D and PTH concentrations. One child, from whom a sample of bone (from a corrective osteotomy) was available for histological examination, showed markedly thickened osteoid seams, characteristic of rickets. All the rachitic children had a calcium intake of less than 150 mg daily. Treatment of these rachitic children with calcium gluconate (1 g/d) led to clinical, radiological, and biochemical healing of rickets. We conclude that rickets in Nigerian children is not due to vitamin D deficiency, but to a lack of calcium. This observation has implications regarding the pathogenesis, treatment, and prevention of rickets/osteomalacia in Nigeria and possibly other African and tropical countries.
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PMID:Rickets in Nigerian children: a consequence of calcium malnutrition. 198 79

Parathyroid hormone-like peptide (PLP) is elaborated from certain tumors and is thought to play a role in the etiology of humoral hypercalcemia of malignancy. The amino-terminal portion of this peptide has a sequence homology with parathyroid hormone PTH. We have compared the agonist potency of the synthetic human amino-terminal 1-34 peptide [human (h)PLP-(1-34)] with that of intact PTH and its amino terminal fragment [hPTH-(1-34)] in the renal and metatarsal cytochemical bioassays (CBA). Furthermore, the antagonist activity of the truncated amino terminal molecule [hPLP-(3-34)] has been compared to that of [Norleu8.18,Tyr34]bovine PTH-(3-34)NH2, and we have also tested their ability to stimulate enzyme activities thought to be associated with bone formation and resorption. In the renal CBA, both PLP-(1-34) and hPTH-(1-34) were equipotent with intact hPTH. In the metatarsal CBA, although the two amino-terminal peptides were equipotent, they elicited an earlier response than the intact PTH molecule. In both assay systems the truncated PLP analog [hPLP-(3-34)] was a more potent antagonist of both PTH and PLP activity than was [Norleu8.18,Tyr34]bovine PTH-(1-34)NH2. In acute studies, hPLP-(1-34) and hPTH-(1-34) stimulated alkaline phosphatase and glucose 6-phosphate dehydrogenase activity in osteoblasts to a similar extent, and both peptides stimulated tartrate-resistant acid phosphatase and succinate dehydrogenase activity in osteoclasts. Longer exposure to the peptides resulted in stimulation of enzyme activity in osteoclasts but not osteoblasts, although there was no difference in potency between the two molecules.
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PMID:Bioactivity of parathyroid hormone and parathyroid hormone-like peptide: agonist and antagonist activities of amino-terminal fragments as assessed by the cytochemical bioassay and in situ biochemistry. 200 12

To examine the possible involvement of IL-6 in bone metabolism, a mouse osteoblastic cell line (MC3T3-E1) and primary osteoblast-like cells from fetal mouse calvaria were cultured with several systemic and local bone-resorbing agents and their expression of IL-6 mRNA was determined. Local bone-resorbing agents such as IL-1 alpha, IL-1 beta, TNF-alpha, and LPS greatly induced IL-6 mRNA expression in both MC3T3-E1 cells and primary osteoblast-like cells. Parathyroid hormone slightly increased expression of IL-6 mRNA in primary osteoblast-like cells but not in MC3T3-E1 cells. Neither IL-6 nor 1 alpha,25-dihydroxyvitamin D3 increased expression of IL-6 mRNA in either of the osteoblast-like cells. In agreement with the expression of IL-6 mRNA, biologically active IL-6 was produced in response to the treatment with IL-1 alpha, TNF-alpha, and LPS in MC3T3-E1 cells. Adding IL-6 dose dependently stimulated the release of 45Ca from prelabeled fetal mouse calvaria. Simultaneously adding suboptimal concentrations of IL-6 and IL-1 alpha induced bone resorption cooperatively. In accord with the increase in the release of 45Ca by IL-6, there were three times as many osteoclasts in the bone sections of calvaria cultured with IL-6 for 5 days as in the controls. IL-6 slightly suppressed alkaline phosphatase activity and collagen synthesis in MC3T3-E1 cells. These results indicate that IL-6 is also produced by osteoblasts, preferentially in response to local bone-resorbing agents, and it induces bone resorption both alone and in concert with other bone-resorbing agents.
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PMID:IL-6 is produced by osteoblasts and induces bone resorption. 212 24

Among several bioactive substances known as coupling factors, transforming growth factor-beta (TGF-beta), interleukin-1 (IL-1), and prostaglandin (PG) E1 and E2 increased not only the activity of alkaline phosphatase but also the rate of incorporation of 45Ca2+ into ROS 17/2.8 during a 3-day culture: the former two factors are known to be formed at the site where bone is resorbed, while PG's are known as one of the factors involved in bone resorption. Parathyroid hormone, another hormone that affects bone metabolism, elevated the incorporation of 45Ca2+ by and decreased the alkaline phosphatase activity of the cells. The facts indicate the possibility that the osteoblastic cells are involved in the transport of calcium ions when bones are being resorbed. On the other hand, when these osteosarcoma cells were cultured in DMEM containing ascorbate and beta-glycerophosphate, followed by staining with silver nitrate by the procedure of von Kossa, there appeared many groups of cells that were positively stained as dark brown spots. Cells were then cultured under the same conditions in the presence of radioactive calcium, and the radioactivity accumulated was measured. The result showed that the presence of both ascorbate and beta-glycerophosphate in the culture medium dramatically increased the accumulation of 45Ca2+. It appears from these facts that ROS 17/2.8 cells are capable of incorporating and/or accumulating calcium ion if they are cultured under appropriate conditions. These cells will probably be able to produce a calcified matrix in vitro.
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PMID:[Effects of L-ascorbic acid and bone metabolism factors on alkaline phosphatase activity of and 45Ca2+ incorporation by ROS 17/2.8 cells]. 213 81

Parathyroid hormone (PTH) has been proposed as a skeletal activator for cyclical protocols of treatment for osteoporosis; among several potential drugs that might serve to depress the subsequent phase of osteoclastic bone resorption, calcitonin is the most selective. Twenty patients aged 50-78 years were enrolled in a study of their biochemical responses during a 14-day activation cycle with synthetic hPTH 1-38, given as a subcutaneous injection of 400 IU/day; half the patients were randomly allocated to receive a subsequent 56-day depressor cycle with calcitonin in a dose of 100 U/day, while the remainder received no further treatment. All patients received an initial 24-h intravenous infusion of hPTH 1-38 (0.5 U/kg/h) to evaluate the PTH-dependent renal synthesis of 1,25(OH)2D. Serum calcium increased from 2.20 +/- 0.07 mmol/l to 2.56 +/- 0.16 (P less than 0.005) during PTH infusion, but was not significantly different from baseline during intermittent treatment. Baseline concentrations of serum 1,25(OH)2D were 22.8 +/- 8.2 pg/ml, increased to 52.2 +/- 25.1 (P less than 0.005) during infusion and remained significantly higher than baseline after 14 days intermittent therapy (33.1 +/- 19.4, P less than 0.05). Gastrointestinal absorption of 45Ca, as represented by alpha (peak fractional absorption/h), increased from 0.397 +/- 0.173 to 0.552 +/- 0.210 (P less than 0.01) during hPTH 1-38 therapy and was moderately correlated with the increment in serum 1,25(OH)2D levels (r = 0.5, P less than 0.03). Daily calcium excretion was significantly increased above baseline during hPTH 1-38 therapy, but there were no correlations between changes in urinary calcium, alpha or serum 1,25(OH)2D levels. Baseline fasting urinary excretion of OH-proline increased during hPTH 1-38 treatment from 30.5 +/- 13.9 mol/mmol creatinine to 43.4 +/- 17.5 immediately after hPTH 1-38 infusion (P less than 0.025), and mean excretion was persistently higher than baseline during intermittent treatment; the increased urine calcium and OH-proline excretion are consistent with PTH-induced activation of bone resorption. Serum alkaline phosphatase and osteocalcin levels increased significantly during a 90-day period of observation after the hPTH 1-38 cycle, which is consistent with increased osteoblast activity in association with coupled bone formation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Biochemical responses to sequential human parathyroid hormone (1-38) and calcitonin in osteoporotic patients. 216 92


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