Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The availability of specific cDNA probes to the chick intestinal calbindin-D28K (CaBP) mRNA has allowed us to assess the regulation of this mRNA in response to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) administration. It has previously been demonstrated that dietary calcium and phosphorus can effect alterations in the steady-state intestinal levels of chick CaBP. We have examined whether or not perturbations in dietary calcium and phosphorus have an effect on the expression of the intestinal mRNA coding for CaBP in the vitamin D-replete chick. We found altered protein levels of CaBP as expected; however there was surprisingly no difference in steady-state CaBP mRNA levels between the different dietary groups. These data suggest that calcium and phosphorus regulation of CaBP occurs at a post-transcriptional level. In addition, we have examined what effect dietary manipulations of calcium and phosphorus levels have on the response of the vitamin D-replete intestine to 1,25(OH)2D3 administration as assessed by CaBP mRNA changes. Administration of 1,25(OH)2D3 to vitamin D-replete chicks maintained on normal calcium and phosphorus levels resulted in a less than 2-fold increase in CaBP mRNA levels. Previous studies have demonstrated that receptor occupancy goes up 6-fold under these conditions; therefore there is apparently a very tight regulation of CaBP gene activity. 1,25(OH)2D3 administration to chicks raised on either low calcium, high calcium, or low phosphorus vitamin D-replete diets similarly showed only small changes in the intestinal CaBP mRNA levels; however there seemed to be qualitative differences in response attributable to the dietary alterations.
Mol Cell Endocrinol 1987 Dec
PMID:Expression of calbindin-D28K mRNA as a function of altered serum calcium and phosphorus levels in vitamin D-replete chick intestine. 369 57

The effects of vitamin D and cholesterol-rich diets on rat aortas were examined. Examination by electron microscopy showed a widening of the subendothelial space and the presence in this space of amorphous substances as early as the second week into mild hypercholesterolemia. After further time elapsed, basement membrane-like substances, microfilaments, migration of mononuclear cells, and modified smooth muscle cells were seen in the subendothelial space. In the vitamin D group, the main electron microscopic finding was of medial smooth muscle cell changes, such as focal degeneration and matrix vesicles. However, calcification was not observed in our present study. In rats fed a cholesterol-rich diet plus vitamin D, changes associated with both the cholesterol-rich diet only and vitamin D only were seen.
Exp Mol Pathol 1986 Jun
PMID:Aortic changes induced by hypercholesterolemia and hypercalcemia in rats. 372 Sep 18

The influence of vitamin D nutrition on melanogenesis in skin induced by UV radiation was studied in pigmented adult rats. Melanogenesis, assessed by the activity of skin tyrosinase (radiometric assay), was studied in vitamin-D-deficient and vitamin-D-fed rats exposed to UV (0.1 J/cm2, 290-320 nm). The tyrosinase activity in skin was not significantly changed by vitamin D treatment alone. In contrast, the induction of tyrosinase activity provoked by UV radiation was greater in vitamin-D-fed than in vitamin-D-deficient rats. The increase in skin tyrosinase activity in response to UV was preceded by an increase in skin cAMP levels. This rise in cAMP was greater in vitamin-D-treated rats than in vitamin-D-deficient rats. The pretreatment of rats with phosphodiesterase inhibitor potentiated the effect of vitamin D on skin tyrosinase activity. The low serum calcium levels in the vitamin-D-deficient group were evidently not responsible for the lower UV induction of skin tyrosinase activity because the vitamin-D-deficient rats with normal serum calcium levels (supplemented with 20% lactose and 2% calcium in the diet) were also unable to show maximal induction of skin tyrosinase activity in response to UV radiation requires the presence of adequate vitamin D. cAMP may be involved in the mediation of this effect. The relationship observed between the vitamin D status of animals and tyrosinase activity of skin could provide an effective feed-back control for protection against UV and vitamin D intoxication.
Mol Cell Endocrinol 1982 Mar
PMID:Vitamin D nutrition increases skin tyrosinase response to exposure to ultraviolet radiation. 617 46

D vitamins are effective inhibitors of the in vitro intraerythrocytic growth of Plasmodium falciparum. Disappearance of the parasitemia was observed after 48 h contact between infected cells and 5 x 10(-6) M 1 alpha-hydroxycholecalciferol, 5 x 10(-5) M 25-hydroxycholecalciferol (25-OH-D-3), 1 alpha, 25-dihydroxycholecalciferol or 2.5 x 10(-4) vitamin D-2 and D-3. A 48 h pretreatment of healthy erythrocytes with 5 x 10(-5) M 25-OH-D-3 did not change their susceptibility to invasion by the parasite and their ability to support the growth of P. falciparum. Ionomycin, a calcium ionophore, and EGTA prevented parasite development at concentrations greater than 2 x 10(-7) M and 4 x 10(-4) M, respectively, but did not antagonize the inhibitory activity of 25-OH-D-3. Addition of 25-OH-D-3 for 12 or 24 h duration to synchronized cultures, showed that the drug had a schizonticidal action, but was without effect when parasites were in the ring form.
Mol Biochem Parasitol 1982 Mar
PMID:Inhibition of the in vitro growth of Plasmodium falciparum by D vitamins and vitamin D-3 derivatives. 628 44

Both 1,25-dihydroxycholecalciferol (1,25(OH)2D3) and 24,25-dihydroxycholecalciferol (24,25(OH)2D3) exerted direct effects on Ca2+ transport and accumulation in primary cultures of bone cells. The following changes were recorded. (1) A significant decrease in the amount of intracellular exchangeable Ca2+. (2) A marked increase in the rate constants of efflux from the 'slow'-turnover intracellular Ca pool. (3) A marked increase in the 'initial rate' of Ca influx into the cells. Thus, vitamin D metabolites caused an increase in the turnover of Ca2+ in bone cells and altered the steady-stae level of intracellular exchangeable Ca2+. Whereas the changes in the rate of efflux were abolished in the presence of inhibitors of protein synthesis, the increase in the rate of influx was not sensitive to these inhibitors. It is suggested that the changes in the two fluxes were mediated by different mechanisms and that the changes in influx were due to a direct effect of vitamin D metabolites on the cellular membranes.
Mol Cell Endocrinol 1980 Sep
PMID:Effects of vitamin D metabolites on cellular Ca2+ and on Ca transport in primary cultures of bone cells. 696 36

Hypophysectomy of animals given maintenance levels of vitamin D and adequate levels of dietary calcium and phosphorus brings about a marked reduction in plasma 1,25-dihydroxyvitamin D3 levels and a significant elevation in plasma 24,25-dihydroxyvitamin D3 levels. The hypophysectomy, as expected, results in reduced growth and lowered plasma levels of inorganic phosphorus. The injection of growth hormone markedly increases plasma levels of 1,25-dihydroxyvitamin D3 in hypophysectomized animals while bringing about a reduction in 24,25-dihydroxyvitamin D3 levels. These results support the idea that the hypophysis plays a role in the regulation of vitamin D metabolism and that growth hormone either directly or indirectly is one of the hypophyseal factors bringing about this regulation.
Mol Cell Endocrinol 1981 Sep
PMID:Role of the hypophysis in the regulation of vitamin D metabolism. 697 64

Residues located between amino acids 244 and 263 in the human vitamin D receptor (hVDR) show extensive homology with other members of the steroid/thyroid/retinoid hormone receptor superfamily. The corresponding region of the glucocorticoid receptor has been shown to interact with the 90-kilodalton heat shock protein (hsp90), yet hVDR does not appear to bind to hsp90. Herein we report a study of hVDR in which the functional role of five conserved residues was tested by replacing Phe-244, Lys-246, Leu-254, Gln-259, and Leu-262 with glycines by site-directed mutagenesis. Initial screening of these mutants indicated that all were significantly impaired in their ability to activate transcription from a vitamin D-responsive reporter construct when expressed in transfected VDR-deficient COS-7 cells. Further characterization revealed two classes of mutants: the predominant class binds the 1,25-dihydroxyvitamin D3 ligand normally but is defective in its ability to form a heterodimeric complex with the retinoid X receptor (RXR) on a vitamin D responsive element (VDRE). A second unique class, represented by a single mutant at Lys-246, is normal both with respect to ligand binding and complex formation but still very impaired in transactivation ability. The distinction between these two classes was confirmed by the demonstration that a member of the first class, with a mutation at Gln-259, could be restored to near wild type transactivation ability by supplying excess RXR, while the Lys-246 mutant could not be so rescued. We therefore conclude that the primary function of this conserved domain in hVDR is the mediation of heterodimerization with RXR, leading to VDRE binding and transactivation. The possibility also exists that the Lys-246 mutant may be impaired in a step of transactivation that is distal to complex formation with RXR on the VDRE, perhaps in interactions with the transcriptional machinery itself.
Mol Endocrinol 1995 Sep
PMID:A highly conserved region in the hormone-binding domain of the human vitamin D receptor contains residues vital for heterodimerization with retinoid X receptor and for transcriptional activation. 749 Nov 9

We demonstrated previously that vitamin D metabolites modulate the response of bone and cartilage cells to 17 beta-estradiol (E2) and dihydrotestosterone (DHT) both in cell cultures and in vivo. In the present study, we investigated to what extent pretreatment with 1,25(OH)2D3 or 24,25(OH)2D3 would reduce the minimal effective dose of E2, DHT or progesterone (P) required for stimulation of DNA synthesis and creatine kinase specific activity in cultured osteoblast-like ROS 17/2.8 cells and in rat embryo epiphyseal cartilage cells, and to what extent such pretreatment would increase the maximal response. We measured responses to sex steroids after pretreatment of the cells for 5 days with 0.02% ethanol vehicle or with the vitamin D metabolites 1,25(OH)2D3 (0.12 nM), or 24,25(OH)2D3 (1.2 nM) singly or in combination. Pretreatment of ROS 17/2.8 cells with 1,25(OH)2D3, but not 24,25(OH)2D3, increased synergistically their response to E2 but not to P, and did not affect their lack of response to DHT. Pretreatment of epiphyseal cartilage cells with either 1,25(OH)2D3 or 24,25(OH)2D3 increased synergistically their DNA synthetic response to all three steroids, but their CK response only to E2 or DHT. The minimal dose for causing a significant response to E2 in ROS 17/2.8 cells or to either E2 or DHT in epiphyseal cartilage cells was reduced 10-fold after pretreatment with vitamin D metabolites. After pretreatment, the maximal response was more than doubled in ROS 17/2.8 cells; epiphyseal cartilage cells showed a similar 10-fold decrease in the dose required for maximal response to E2 or DHT; the improvement in the response to P was significant only for DNA synthesis. We conclude that pretreatment with the appropriate vitamin D metabolite(s) both reduces by an order of magnitude, or more, the amount of sex steroids needed to stimulate skeletal derived cells and increases synergistically the maximal response of the cells.
J Steroid Biochem Mol Biol 1995 Nov
PMID:Pretreatment with 1,25(OH)2 vitamin D or 24,25(OH)2 vitamin D increases synergistically responsiveness to sex steroids in skeletal-derived cells. 749

Nitric oxide (NO) modulates the activity of a number of cell types, but little is known about its possible role in bone metabolism. In the present study we demonstrate that freshly isolated murine osteoblasts and an osteoblastic cell line express NO-synthase mRNA and release NO when stimulated with IL-1 or LPS, thus confirming the results of some recent reports using human and rat osteoblast-like cells. Synergistic effects were found between IL-1 and LPS or TNF. Enzyme induction was blocked by dexamethasone and IL-4. 1,25-dihydroxyvitamin D3 did not modify basal NO synthesis, but it markedly increased the cytokine-induced NO release. M-CSF, GM-CSF, IL-3, LIF, PTH, estradiol and calcitonin did not show significant effects on NO synthesis. NOS induction was blocked by various tyrosine-kinase inhibitors, geldanamycin and herbimycin A being the most potent. These results suggest that endogenous NO might participate in the regulation of bone remodeling at the local level, and may mediate some effects of vitamin D on bone. NO has recently been reported to inhibit osteoclastic bone resorption. The release of NO induced by bone-stimulating factors such as IL-1 may represent a protective mechanism helping to avoid excess resorption and preserve bone integrity in inflammatory conditions.
Mol Cell Endocrinol 1995 Jan
PMID:Mechanisms controlling nitric oxide synthesis in osteoblasts. 754 Sep 93

Vitamin D3 administration affects the NAD-linked oxidoreductase activities of Krebs cycle from intestinal mucosa of vitamin D-deficient chicks. Vmax values were increased in all of them, while K0.5 for substrate remained unchanged except for 2-oxoglutarate dehydrogenase, which showed lower affinity for oxoglutarate. Addition of Ca2+ to the incubation medium increased the affinity of 2-oxoglutarate dehydrogenase and NAD-isocitrate dehydrogenase for their substrates either in the vitamin D3 treated group or in the control one. The activity of succinate dehydrogenase, a FMN-dependent oxidoreductase, was not modified by vitamin D3 administration. The oxygen consumption of the intestinal mitochondria was not altered by cholecalciferol treatment to vitamin D-deficient chicks. The reason why vitamin D3 selectively affects the NAD-linked oxidoreductase activities of the Krebs cycle remains unknown. The vitamin D hormone, 1,25(OH)2D3, appears to be the mediator of the response.
Biochem Mol Biol Int 1995 Jul
PMID:Vitamin D affects Krebs cycle NAD-linked oxidoreductases from chick intestinal mucosa. 754 52


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