Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Stanniocalcin is a calcium- and phosphate-regulating glycoprotein hormone that was first described in fish where it functions in preventing hypercalcemia. Human cDNA clones encoding the homolog of stanniocalcin have been recently isolated. In this study, the full-length cDNA coding for human stanniocalcin (hSTC) was cloned into both baculovirus and CHO expression vectors. Recombinant hSTC was then produced efficiently from both baculovirus-infected insect cells and CHO cells in large-scale bioreactors. Purification protocols were developed and used to purify recombinant hSTC from both sources in four chromatography steps. The hSTCs from both expression systems were secreted as glycosylated proteins and as disulfide-linked homodimers. The results from glycosylation studies indicated that stanniocalcin from both sources contained N-linked oligosaccharides but no O-linked sugars. In an in vivo bioassay based on the inhibition of gill calcium transport in fishes, the baculovirus and CHO-expressed protein showed biological activity which is dose dependent. The inhibitory effects of hSTC produced from both systems were essentially equipotent in fishes, despite the differences in glycosylation. Consequently, the precise role of the carbohydrate moiety in recombinant hSTC remains to be determined.
 ...
PMID:Expression, purification, and bioassay of human stanniocalcin from baculovirus-infected insect cells and recombinant CHO cells. 953 7

Stanniocalcin (STC) is a glycoprotein hormone first found in fish, in which it regulates calcium homeostasis and protects against hypercalcemia. Human and mouse stc cDNA were recently cloned. We found a dramatically upregulated expression of STC during induced neural differentiation in a human neural crest-derived cell line, Paju. Immunohistochemical staining of sections from human and adult mouse brain revealed abundant presence of STC in the neurons with no activity in the glial cells. STC expression was not seen in immature brain neurons of fetal or newborn mice. Given that STC has been found to regulate calcium/phosphate metabolism in some mammalian epithelia, we suggest that STC may act as a regulator of calcium homeostasis in terminally differentiated brain neurons.
 ...
PMID:High expression of stanniocalcin in differentiated brain neurons. 970 4

Bony fish use the glycoprotein hormone stanniocalcin (STC) to counteract hypercalcaemia. This is achieved through dual mechanisms involving gill calcium uptake inhibition and stimulation of renal inorganic phosphate reabsorption. Human STC (hSTC-1) shows considerable homology with both rat and mouse STC (mSTC) and their mRNA is expressed in a wide range of tissues. In fish, STC is produced by endocrine glands known as the corpuscles of Stannius but in mammals the widespread expression is suggestive of a paracrine rather than an endocrine role. In order to determine the distribution and strucutral characteristics of hSTC-1, the recombinant protein was expressed in bacteria, purified by metal-ion affinity chromatography, and a study was made of the likely epitopes for raising an antibody. This novel hSTC-1 antibody was used to test the purification protocol. Since the role of mammalian STC is largely unknown, the specific distribution of STC needed to be addressed. To test the specificity of the antibody, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)/Western blotting was undertaken in homogenised rat bladder, ovary and kidney.
 ...
PMID:Expression and localisation of stanniocalcin 1 in rat bladder, kidney and ovary. 1045 Nov 17

Stanniocalcin (STC) is a glycoprotein hormone originally found in bony fish, in which it regulates calcium/phosphate homeostasis and protects against hypercalcemia. The recently characterized human STC shows about 70% homology with fish STC. We previously reported a constitutive expression of STC in terminally differentiated neurons. Here, we show that exposure of human neural-crest-derived cell line Paju to hypercalcemic culture medium induced expression of STC. Treatment of Paju cells with recombinant human STC increased their uptake of inorganic phosphate. Paju cells expressing STC by cDNA transfection displayed increased resistance to ischemic challenge and to elevated intracellular free calcium induced by treatment with thapsigargin. An up-regulated and redistributed expression of STC was observed in neurons surrounding the core of acute infarcts in human and rat brains. Given that mobilization and influx of calcium is considered a main neurotoxic mechanism following ischemia, our results suggest that the altered expression of STC contributes to the protection of cerebral neurons against hypoxic/ischemic damage. Manipulation of the STC expression may therefore offer a therapeutic approach to limit the injury after ischemic brain insults.
 ...
PMID:Stanniocalcin: A molecular guard of neurons during cerebral ischemia. 1072 97

Parathyroid gland is the overall regulatory organ within the systemic calcium homeostasis. Through cell surface bound calcium-sensing receptors external calcium inversely regulates release of parathyroid hormone (PTH). This mechanism, which is voltage independent and most sensitive around physiologic calcium concentrations, is regulated through a 120 kDa calcium sensing receptor, CaR. Inherited inactivation of this receptor is the cause for familial hypocalciuric hypercalcemia (FHH). Parallel research identified the 550 kDa glycoprotein megalin, which also is expressed on the parathyroid cell surface, as another potential calcium sensing protein. Although this protein expresses numerous calcium binding sites on its external domain, its main function may be calcium sensitive binding and uptake of steroid hormones, such as 25-OH-vitamin D3 (bound to vitamin D binding protein) and retinol. In hyperparathyroidism (HPT), excessive PTH is secreted and the calcium sensitivity of the cells reduced, i.e. the set-point, defined as the external calcium concentration at which half-maximal inhibition of PTH release occurs, shifted to the right. Pathological cells have reduced expression of both CaR and megalin, and reduced amount of intracellular lipids, possibly including stored steroid hormones. A number of possible genetic disturbances have been identified, indicating multifactorial reasons for the disease. In postmenopausal women, however, the individual group with highest incidence of disease, a causal relation to reduced effect of vitamin D is possible. An incipient renal insufficiency with age, lack of sunshine in the Northern Hemisphere, and an association to the baT haplotype of the vitamin D receptor supports this theory. This review summarizes data on regulation of PTH release, dysregulation in HPT, as well as proliferation of parathyroid cells.
 ...
PMID:Pathophysiology of primary hyperparathyroidism. 1080 83

Stanniocalcin (STC) is a 28 kD glycoprotein hormone originally found in bony fish in which it regulates calcium/phosphate homeostasis and protects against hypercalcemia. The recently characterized mammalian STC shows about 70% homology with fish STC. The epithelial cells of proximal tubuli in human and rat kidney and brain neurons have been found to express STC. Here we show that the epithelium of the choroid plexus, already at 16 weeks of fetal age, and of plexus papillomas, synthesize and express STC. Our findings suggest that STC may be of importance for the distribution of calcium and phosphate between the cerebrospinal fluid and blood.
 ...
PMID:Expression of stanniocalcin in the epithelium of human choroid plexus. 1113 38

Stanniocalcin-1 (STC) is a 56-kDa homodimeric glycoprotein hormone originally found in fish, in which it regulates calcium/phosphate homeostasis and protects against toxic hypercalcaemia. The recently characterized human STC is 80% similar to fish STC. We have earlier reported a high expression of STC in terminally differentiated human and rodent brain neurones, and found that STC contributes to the maintenance of their integrity. Here, we report that mature megakaryocytes and platelets display high STC content. K562 cells, induced to megakaryocytoid differentiation in vitro, acquired expression of STC, which was not seen in untreated K562 cells or cells induced to erythroid differentiation.
 ...
PMID:Expression of stanniocalcin-1 in megakaryocytes and platelets. 1240 69

Vascular calcification is the most common type of extra-osseous calcification in end-stage renal disease (ESRD), manifesting as both medial and intimal calcification of large arteries. It is highly prevalent, often progressive and is associated with reduced arterial elasticity and increased mortality. Risk factors for calcification in ESRD include age, duration of dialysis, diabetes mellitus, most probably an elevated calcium-phosphorus product (Ca x P) level, the dose of calcium-containing phosphate binders and the induction of the systemic inflammatory response. Uraemic calcification was thought to be a largely physico-chemical process facilitated by elevated Ca x P (i.e. "metastatic" calcification). It is now well established, however, that vascular smooth muscle cells actively take up phosphate to form bioapatite. This process is associated with a phenotypic transformation of vascular smooth muscle cells during which they express osteoblast markers. In addition to phosphate, various other factors are likely to increase bioapatite formation, e.g. lipids and inflammatory cytokines. There have also been relatively new insights relating to the role of endogenous inhibitors of calcification [i.e. matrix Gla protein and fetuin-A (alpha(2)-Heremans-Schmid glycoprotein)], in particular the downregulation of fetuin-A in systemic inflammation. Decreased serum fetuin-A has been shown to be associated with a reduced capacity to inhibit calcium phosphate precipitation in vitro and is predictive of mortality in dialysis patients. These new insights into pathogenesis may lead to better prevention and treatment of calcification (e.g. with calcimimetics, anti-cytokines, etc.). However, the only preventive approach to have been established prospectively to date is the replacement of calcium-containing phosphate binders with sevelamer HCl, a non-calcaemic phosphate binder. Yet, it remains unclear whether sevelamer HCl reduces vascular calcification by preventing episodes of hypercalcaemia and/or by reducing low-density lipoprotein (LDL)-cholesterol levels.
 ...
PMID:Vascular calcification in patients with end-stage renal disease. 1577 77

In acute myeloid leukemia (AML), cell proliferation and differentiation are uncoupled, causing a maturation block. Induction of terminal differentiation is a potential therapeutic strategy. 1alpha, 25(OH)2 Vitamin D3 regulates differentiation and is immunomodulatory at concentrations causing severe hypercalcemia, thus limiting its use. We investigated 1alpha, 25(OH)2 Vitamin D3 and 5 of its more potent analogs with reduced calcium resorbing activity for differentiation of blast cells from AML (FAB M1) patients, compared to TPA. Blast phenotype, p-glycoprotein expression, cytokine production, and lineage specificity were examined. The Vitamin D3 analogs had no effect on cell viability and proliferation. They induced incomplete differentiation, with increase in AP, NSE and NBT positivity of cells, but no cell sticking and spreading as observed with TPA. The analogs were more effective than the parent compound. They also inhibited the production of IL-6 and IL-8. Vitamin D3 and its analogs can induce differentiation of primary cells from AML patients in vitro, but may need to be combined with other agents for terminal differentiation of blasts and effective therapy in vivo.
 ...
PMID:Effect of 1,25(OH)2 Vitamin D3 analogs on differentiation induction and cytokine modulation in blasts from acute myeloid leukemia patients. 1537 Feb 59

Stanniocalcin (STC) is a glycoprotein hormone originally found in teleost fish, where it regulates the calcium/phosphate homeostasis, and protects the fish against toxic hypercalcemia. STC was considered an exclusive fish protein, until the cloning of cDNA for human (in 1995) and murine (in 1996) STC. We originally reported a high constitutive content of STC in mammalian brain neurons, and found that the expression of STC occurred concomitantly with terminal differentiation of neural cells. Since then, we have investigated the expression of STC in relation to terminal cell differentiation also in mammalian hematopoietic tissue, and fat tissues. In this review we summarize our findings on STC expression during postmitotic differentiation in three different cell systems; in neural cells, in megakaryocytes and in adipocytes. We also present findings, suggesting that STC plays a role for maintaining the integrity of terminally differentiated mammalian cells.
 ...
PMID:Stanniocalcin in terminally differentiated mammalian cells. 1547 32


<< Previous 1 2 3 Next >>