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

We have previously reported that the amount of epidermal calcium binding protein (ECaBP) in the skin decreases in the absence of vitamin D. Since vitamin D influences epidermal differentiation, and the synthesis of ECaBP may vary with cell differentiation, it was necessary to know whether vitamin D acts directly on the translational or post-translational level of ECaBP synthesis or indirectly by its action on epidermopoiesis. The cell-free translation technique was used to demonstrate the presence of mRNA coding for ECaBP. The activity of this mRNA has been evaluated in the skin of vitamin D-fed and in vitamin D-deficient rats with or without treatment with 1,25-dihydroxycholecalciferol (1,25(OH)2D3). Vitamin D deficiency decreased the ECaBP mRNA activity. The latter was selectively increased in animals given a single dose of 1,25(OH)2D3. These results suggest that 1,25(OH)2D3 stimulates the production of ECaBP mRNA or stabilizes this mRNA.
Mol Cell Endocrinol 1988 Dec
PMID:Effect of vitamin D deficiency and 1,25-dihydroxycholecalciferol treatment on epidermal calcium-binding protein (ECaBP) RNA activity. 306 67

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

1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] stimulates the alkaline phosphatase of rat and human osteoblast-like cells in culture. Here the mechanism of this effect was investigated using the rat osteogenic sarcoma cell line ROS 17/2-8. We found that 50% maximum alkaline phosphatase stimulation is elicited by 1,25(OH)2D3 at 7 X 10(-10) M. The concentration of serum in the culture medium influences inversely the effective 1,25(OH)2D3 concentration. Increased alkaline phosphatase appears after a lag period of cell exposure to 1,25(OH)2D3 which is between 8 and 24 h; during 96 h culture in the presence of 1,25(OH)2D3 the enzyme activity continues to rise. Cycloheximide (0.1-1 micrograms/ml) added in the cultures for 3 days or actinomycin-D (1-30 ng/ml) added for 24 h inhibit the 1,25(OH)2D3 effect on alkaline phosphatase in a dose-dependent fashion; withdrawal of cycloheximide restores the responsiveness of cells to 1,25(OH)2D3 completely, but withdrawal of actinomycin-D restores cell responsiveness only partially. These findings suggest that 1,25(OH)2D3-induced stimulation of alkaline phosphatase in the osteoblast-like cells involves genome activation and de novo protein synthesis.
Mol Cell Endocrinol 1983 Nov
PMID:Mechanism of action of 1,25-dihydroxyvitamin D3-induced stimulation of alkaline phosphatase in cultured osteoblast-like cells. 635 97

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

1 alpha,25-Dihydroxyvitamin D3 (1,25) is a structurally unique steroid hormone because it not only possesses the complete 25-hydroxycholesterol side chain, but most notably, it possesses a seco-B triene structure (it lacks a B-ring and is usually depicted in a non-steroidal, extended conformation). In contrast, the classical steroid hormones possess a truncated side chain (progesterone, cortisol, and aldosterone) or no side chain (estradiol and testosterone) and they all possess the fully intact ABCD steroid rings. These structural differences render the seco-B-steroid 1,25 considerably more conformationally flexible. Since 1,25 is now known to target a myriad of tissues where specific interactions occur to produce an array of biological responses, it is of interest to determine whether different topologies of 1,25 (resulting from different conformational orientations of 1,25) are necessary to interact effectively at the different target sites. The array of biological responses include both non-genomic and genomic effects and there is considerable promise for the efficacy of 1,25 analogs as chemotherapeutic agents in a variety of human disease states. For the non-genomic calcium transport response of transcaltachia, the finding that two 6-s-cis locked analogs, 1 alpha,25-dihydroxyprevitamin D3 (pre-1,25) and 1 alpha,25-dihydroxylumisterol3 (1,25-Lumi), are equipotent to 1,25, points strongly to the involvement of the 6-s-cis conformer of 1,25 as the biologically active conformer. Since there is a continuum of easily interconvertible 6,7-single bond conformers of the seco-B ring available to 1,25, conformational minima (either local or global) may have little to do with the manner in which 1,25 is bound to receptor. For the genomic calcium transport response, and for other genomic (or non-genomic) effects, there is no clear evidence whether the steroidal (s-cis) or non-steroidal (s-trans) conformer of 1,25 is involved. In order to address this matter further, efforts are underway to evaluate other conformationally locked analogs of 1,25 which might mimic either the planar 6-s-trans-1,25 or some intermediate conformer between it and the planar-6-s-cis form.
J Steroid Biochem Mol Biol 1995 Jun
PMID:Chemistry and conformation of vitamin D molecules. 762 17

Intestinal Ca absorption from the diet consumed during one night was measured in male rats fed a normal (0.5%) Ca, low fiber (3% cellulose) diet by determining the decrease in 47Ca/47Sc ratio between diet and feces. One-half of the rats had been cecectomized 9 weeks previously at 14 weeks of age. Calcitriol injections, given intraperitoneally the morning of the experiment, stimulated fractional intestinal Ca absorption 2.5-fold in intact rats (16.9 +/- 2.0% to 42.2 +/- 1.8%) and 2.3-fold in cecectomized rats (20.1 +/- 1.4% to 46.8 +/- 1.2%). Similar results were obtained when the data were calculated in terms of total Ca absorption expressed as mg/day. Thus, although the cecum can absorb Ca when diets contain large amounts of digestible fiber, cecectomy does not influence the stimulation of intestinal Ca absorption induced by calcitriol in vitamin D-replete rats fed a low fiber diet.
J Steroid Biochem Mol Biol 1995 Jul
PMID:The cecum does not participate in the stimulation of intestinal calcium absorption by calcitriol. 763 18

Recent studies have provided evidence indicating that 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] rapidly stimulates calcium influx through Ca2+ channels in isolated chick heart tissue and cells. Studies were performed both to evaluate the characteristics of the hormone action in cultured myocytes and to obtain information on the metabolic pathway which mediates its effects. Treatment of 70-80% confluent chick embryo myocyte monolayers with 1,25(OH)2D3 induced a fast (within 3-5 min) stimulation of 45Ca uptake which was dose-dependent, maximum responses (130% above controls) being elicited at a concentration of 10(-10) M. Physiological levels of 25(OH)D3 and 24,25(OH)2D3, and the synthetic analog 1 alpha (OH)D3, had lower activity. Coincident with the rapid changes in Ca uptake, 1,25(OH)2D3 significantly increased cAMP levels. The hormone-induced increase in cAMP was not blocked by nifedipine. Compound SQ 22536, a specific inhibitor of adenylate cyclase, completely suppressed the effects of the sterol on cAMP and Ca uptake. Furthermore, GDP-beta-S inhibited the increase in Ca uptake by 1,25(OH)2D3. These results involve the adenylate cyclase pathway and the participation of G proteins in 1,25(OH)2D3 stimulation of Ca influx in chick heart cells.
J Mol Cell Cardiol 1994 Dec
PMID:Modulation of calcium uptake in cultured cardiac muscle cells by 1,25-dihydroxyvitamin D3. 773 Oct 54

Sarcoidosis is characterized by the accumulation of activated lymphocytes in the lungs and other organs and by the spontaneous production of the active form of vitamin D, calcitriol. We hypothesized that calcitriol may modulate the responsiveness of human lymphocytes to the relevant biologic mediator, interleukin-2 (IL-2). After culture for 48 h with phytohemagglutinin, human peripheral blood lymphocytes migrated through nitrocellulose filters, secured in microchemotaxis chambers, in response to IL-2. When calcitriol at 1 nM was included in the cultures, the migratory response to IL-2 was completely abrogated. This inhibitory effect was seen despite the fact that cultured lymphocytes continued to express the IL-2 receptor and other activation markers. A similar but more rapid effect could be demonstrated by including calcitriol in the lower well during our 3-h chemokinesis assay. Calcitriol blocked IL-2-induced lymphocyte migration in a dose-dependent fashion. The synthetic noncalcemic vitamin D analogue MC 903 was equally effective in this assay. IL-2-induced migration could also be prevented by the protein kinase C inhibitor H-7, but calcitriol appeared to be at least 1,000 times more potent. Our studies suggest that calcitriol is a potent natural immunomodulator with rapid suppressive effects that may be mediated through protein kinase C. Synthetic analogues such as MC 903 may offer exciting therapeutic opportunities.
Am J Respir Cell Mol Biol 1995 Jun
PMID:Calcitriol and its synthetic analogue MC 903 inhibit the interleukin-2-induced migration of human lymphocytes. 776 30

Three days pretreatment of the prolactin (PRL) secreting GH4C1 cells with 10 nM calcitriol attenuated both the basal and thyrotropin-releasing hormone (TRH)-stimulated (1 microM, 5 s) inositol trisphosphate (IP3) production by 30 and 26%, respectively. The effect was detectable at 10 nM (basal) and 1 pM (TRH-stimulated), and maximal at 1 microM (basal) and 10 nM (TRH), respectively. Calcitriol was at least 100 times more potent than calcidiol and 24-hydroxycalcidiol, and the effect was reversible upon cessation of pretreatment. Calcitriol pretreatment (1 microM, 5 days) also decreased the levels of phosphatidyl-inositol, phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate by 23, 55 and 32%, respectively. GTP gamma S-stimulated (100 microM, 30 s) IP3 production was decreased by 45% after calcitriol pretreatment (10 nM, 5 days). Pertussis toxin (1 nM, 4 h) attenuated both the basal and TRH-stimulated IP3 production, but this effect was omitted by calcitriol pretreatment. Thus, calcitriol specifically attenuates both the basal and TRH-stimulated inositol phosphate production in GH4C1 cells. The mechanism, at least partly, involves decreased availability of phosphoinositides for phospholipase C. Calcitriol regulation of a pertussis toxin-sensitive G-protein might also play some role.
Mol Cell Endocrinol 1993 Jun
PMID:Calcitriol attenuates the thyrotropin-releasing hormone-stimulated inositol phosphate production in clonal rat pituitary (GH4C1) cells. 834 24

To study the direct effects of thyroid hormones on human osteoblasts we examined the effects of triiodothyronine (T3) on proliferation and differentiation of human osteoblast-like (hOB) cells in vitro. T3 increased 3H-thymidine incorporation in DNA of hOB cells (p < 0.05, n = 10). Half maximal effects obtained at a T3 concentration of 1-10 nM which lies within the physiological concentration of the hormone. In addition, T3 increased alkaline phosphatase production (p < 0.05, n = 13) and inhibited procollagen type I carboxyterminal propeptide (PICP) production (p < 0.05, n = 13). T3 interaction with 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) was also studied. 1,25-(OH)2D3 (10(-9)M) alone doubled AP production and induced osteocalcin expression by hOB cells. Concurrent addition of T3 and 1,25-(OH)2D3 did not further increase production of AP, PICP or osteocalcin by hOB cells. In conclusion, T3 exerts significant effects on osteoblast proliferation and differentiation, suggesting that human osteoblasts are targets for thyroid hormones.
Biochem Mol Biol Int 1993 Jul
PMID:Effects of triiodothyronine on DNA synthesis and differentiation markers of normal human osteoblast-like cells in vitro. 840 33


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>