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)

1. The metabolism of an intravenous pulse dose of double-isotope-labelled cholecalciferol has been studied in control subjects with widely differing states of vitamin D nutrition and in patients with primary disorders of parathyroid function. 2. The formation of labelled 1,25-dihydroxy-cholecalciferol [1,25-(OH)2D3] and labelled 24,25-dihydroxycholecalciferol [24,25-(OH)2D3] has been related to the prevailing concentrations in serum of 25-hydroxycholecalciferol [25-(OH)D3], immunoreactive parathyroid hormonel, calcium and orthophosphate (Pi). 3. In control subjects with relative vitamin D deficiency [serum 25-(OH)2D3 was related inversely to the serum 25-(OH)D3 and serum calcium, and directly to serum immunoreactive parathyroid hormone. No formation of 1,25-(OH)2D3 was detectable to form labelled 24,25(OH)2D3 preferentially. 4. No control subject produced significant amounts of both labelled 1,25-(OH)2D3 and labelled 24,25-(OH)2D3 simultaneously. 5. All subjects with primary hyperparathyroidism produced significant amounts of labelled 1,25-(OH)2D3 and labelled 24,25-(OH)2D3 simultaneously; the renal turnover of 25-(OH)D3 was apparently greater than in nutritionally matched controls. Serum labelled 1,25-(OH)2D3 in this disease was not correlated with serum 25-(OH)D3, immunoreactive parathyroid hormone, calcium or Pi. Production of labelled 24,25-(OH)2D3 was inappropriately high for the prevailing nutritional state. 6. The indirectly estimated their concentration of 1,25-(OH)2D3 showed only a fourfold variation in control subjects (45-180 pmol/l), compatible with its having a regulated hormonal function. 7. The data suggest that the production of 1,25-(OH)2D3 from a pulse dose of cholecalciferol is normally regulated, directly or indirectly, by the parathyroid hormone.
Clin Sci Mol Med 1975 May
PMID:Vitamin D metabolism and parathyroid function in man. 16 31

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

Rats were raised in the absence of vitamin D in utero and throughout post-fetal life and neither 1,25-dihydroxyvitamin D3 nor related metabolites were detected in serums. No changes were observed in the relative amount of extractable noncollagenous bone proteins (NCP) in rachitic compared to vitamin-D-repleted animals. As expected, the relative levels of the mineral-bound, serum-derived albumin and alpha 2HS glycoprotein were unaffected in bones of rachitic animals. Interestingly, the vitamin D deficiency also did not have dramatic effects on several bone cell-derived noncollagenous proteins including: bone proteoglycans I & II, bone sialoprotein II osteonectin, and osteocalcin. In contrast to the proteoglycans, the bone sialoprotein II and osteonectin were found in the nonmineral compartment of the rachitic animals, presumably bound to the wide osteoid seam.
Mol Cell Biochem 1987 Apr
PMID:Noncollagenous bone proteins in experimental rickets in the rat. 360 Jun 17

A model of the healing phase of low phosphate, vitamin D deficiency was used to investigate the initial stages of mineralization. The matrix vesicle distribution between the zones of the growth plate was found to be bimodal with high volume densities in the resting and hypertrophic zones and low volume densities in the proliferative and calcifying zones. Healing of the rachitic lesion was associated with a decrease in matrix vesicle volume density in the calcifying zone, compared with the lower hypertrophic zone in florid rickets. The volume density differences were due to differences in the number of vesicles, as the variation in mean caliper diameter was rather small. The findings are compatible with the dynamic cell debris theory for matrix vesicle origin and distribution presented earlier, which favours the view that a major part of matrix vesicles are formed from cell debris. A role of matrix vesicles in the mineralization process is indicated by the finding of an association between mineralization and matrix vesicle degradation.
Virchows Arch B Cell Pathol Incl Mol Pathol 1983
PMID:Stereological studies on matrix vesicle distribution in the epiphyseal growth plate during healing of low phosphate, vitamin D deficiency rickets. 614 59

We have studied two proteins potentially involved in the regulation of the 25-OH-D-1-hydroxylase, which is located in the renal mitochondria and which is responsible for the production of the steroid hormone 1,25(OH)2D3. The endogenous inhibitor of cyclic AMP-dependent protein kinase, PKI, is down regulated by 1,25(OH)2D3. Having cloned and sequenced PKI cDNA, we studied its message levels and found them to be regulated by 1,25(OH)2D3 tissue specifically in the kidney and in kidney cell culture. In other experiments we over expressed the ferredoxin component of the 1-hydroxylase and found it to be physically and chemically indistinguishable from those of classic steroidogenic tissues. The mRNA encoding the ferredoxin component is up-regulated by chronic vitamin D deficiency, which at the same time leads to sustained elevation in 1-hydroxylase activity; no short term effect of 1,25(OH)2D3 on ferredoxin mRNA in kidney cell culture could be demonstrated. Finally, there was an association between decreased phosphorylation of ferredoxin and decreased 1-hydroxylase activity brought about by treatment of cultured kidney cells with TPA. Control of the renal signaling events involved in the production of 1,25(OH)2D3 remains a fruitful area of investigation in the field of the metabolism and actions of vitamin D and its metabolites.
J Steroid Biochem Mol Biol 1995 Jun
PMID:Regulation of the ferredoxin component of renal hydroxylases at transcriptional and postranslational levels and of the protein inhibitor of cyclic AMP-dependent kinase. 762 15

During the fetal and suckling periods of mammalian development, the mother serves as the sole nutritional source for the offspring. As such, the quality of the maternal diet effects growth and development of the offspring during these periods. This study sought to determine if a maternal vitamin D deficiency altered the well characterized development of the neonatal heart. Weaned rat pups (21-day-old) were obtained from mothers who had consumed either a vitamin D-supplemented diet (3000 IU of vitamin D/kg) or a low vitamin D diet (< 200 IU of vitamin D/kg) prior to becoming pregnant and throughout pregnancy and suckling. These pups were sacrificed, hearts excised, and the hearts biochemically analysed for metabolic and contractile protein properties. The pups of dams fed the low vitamin D diet were slightly hypocalcemic relative to those on the supplemented diet (2.28 v 2.41 mumol/l, P < 0.05), had significantly lower body weights (43 v 55 g), heart weights (143 v 174 mg), citrate synthase activity (106 v 147 mumol g-1 min-1), and 3-hydroxyacyl CoA dehydrogenase activity (59 v 91 mumol g-1 min-1). Hexokinase activity (1.98 v 2.02 mumol g-1 min-1), and the distribution of cardiac myosin among its three isoforms (> 85% V1), were unaffected by this dietary deficiency, however myofibrillar protein content was approximately 15% lower in the experimental hearts. These data demonstrate that maternal consumption of a low vitamin D diet results in a general but significant slowing of neonatal cardiac development.
J Mol Cell Cardiol 1995 Jun
PMID:Maternal consumption of a low vitamin D diet retards metabolic and contractile development in the neonatal rat heart. 853 Dec 6

Vitamin D deficiency affects the lipid composition and Ca2+ uptake of intestinal basolateral membranes from chick intestine. The increased cholesterol content causes an increase in the molar ratio cholesterol/phospholipid. Phospholipid classes remain unchanged, but the percentages of arachidonic acid from the from the major phospholipid fractions are increased. After 24 hours of oral administration of 2,000 IU of cholecalciferol to vitamin D-deficient chicks, the cholesterol values do not change, but the amount of arachidonic acid returns to normal values. Ca2+ uptake driven by ATP is diminished in vesicles from intestinal basolateral membranes of vitamin D-deficient chicks. Cholecalciferol treatment returns these values to the controls which might be due mainly to the increased number of Ca2+ pump units. In conclusion, changes in lipid composition and in Ca2+ pump caused by vitamin D deficiency seems to play a role in the decrease of vesicular Ca2+ transport. A single dose of cholecalciferol restores only partially the lipid-protein changes produced by vitamin D deficiency.
Biochem Mol Biol Int 1997 Jun
PMID:Effect of vitamin D deficiency on lipid composition and calcium transport in basolateral membrane vesicles from chick intestine. 923 33

The active, hormonal form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) has numerous pleiotropic actions including the regulation of calcium homeostasis, control of bone cell differentiation and modification of immune responses. Synthesis of 1,25(OH)2D3 from the major circulating metabolite, 25-hydroxyvitamin D3 (25(OH)D3), is catalysed by the mitochondrial cytochrome P450 enzyme 25-hydroxyvitamin D-1alpha-hydroxylase (1alpha-HYD). Although 1alpha-HYD activity has been demonstrated at several ectopic sites, circulating levels of 1,25(OH)2D3 appear to reflect the expression of this enzyme in the kidney. The tight regulation of 1alpha-HYD in both renal and ectopic tissues has made studies of the expression and regulation of this enzyme remarkably difficult. However, the recent cloning of mouse, rat and human cDNAs for 1alpha-HYD has stimulated renewed interest in the molecular endocrinology of 1,25(OH)2D3 production. Analysis of the 1alpha-HYD sequence has revealed homology with the liver enzyme vitamin D-25-hydroxylase, and the ubiquitously expressed vitamin D-24-hydroxylase. Furthermore, mutations causing the inherited disorder vitamin D-dependent rickets type 1, also known as pseudo-vitamin D deficiency rickets have been described for the 1alpha-HYD gene and these have been mapped to chromosome 12q14 by linkage analysis. The availability of sequence information for the 1alpha-HYD gene has also facilitated the development of new molecular tools which will help to clarify key functions of the enzyme. Specific issues such as tissue distribution and regulatory pathways are discussed in this review, with particular emphasis on the role of 1alpha-HYD in renal calcium/phosphate homeostasis.
Mol Cell Endocrinol 1999 May 25
PMID:The renal function of 25-hydroxyvitamin D3-1alpha-hydroxylase. 1041 36

The active form of vitamin D, 1,25-dihydroxvitamin D(3) (1, 25(OH)(2)D(3)), is a pleiotropic hormone whose actions include the regulation of calcium homeostasis, control of bone cell differentiation and modification of immune responses. Synthesis of 1, 25(OH)(2)D(3) from the major circulating metabolite, 25-hydroxyvitamin D(3) (25(OH)D(3)), is catalysed by a mitochondrial cytochrome P450 enzyme, 25-hydroxyvitamin D-1alpha-hydroxylase (1alpha-OHase). Although 1alpha-OHase is expressed predominantly in the kidney, extra-renal production of 1,25(OH)(2)D(3) has also been demonstrated in tissues such as lymph nodes and skin. The tight regulation of 1alpha-OHase which occurs in both renal and peripheral tissues has made studies of the expression and regulation of this enzyme remarkably difficult. However, the recent cloning of mouse, rat and human cDNAs for 1alpha-OHase (CYP1alpha/Cyp1alpha) has enabled a more thorough characterization of this enzyme. In particular, analysis of the CYP1alpha gene has identified mutations causing the inherited disorder vitamin D-dependent rickets type 1, also known as pseudo-vitamin D deficiency rickets. Studies from our own group have focused on the distribution of 1alpha-OHase in both renal and extra-renal tissues. Data indicate that the enzyme is expressed throughout the nephron, suggesting discrete endocrine and paracrine/autocrine functions. Further immunohistochemical analyses have shown that the enzyme is widely distributed in extra-renal tissues, and this appears to be due to the same gene product as the kidney. Collectively, these observations have raised important new questions concerning the role of 1alpha-OHase in vitamin D signalling at a local level. The relationship between expression of protein for 1alpha-OHase and enzyme activity has yet to be fully characterized and may be dependent on membrane proteins such as megalin. Similarly, elucidation of the mechanisms involved in differential regulation of renal and extra-renal 1,25(OH)(2)D(3) production will be essential to our understanding of the tissue-specific functions of 1alpha-OHase. These and other issues are discussed in the current review.
J Mol Endocrinol 2000 Oct
PMID:1alpha-Hydroxylase and the action of vitamin D. 1101 42

Our recent epidemiological study (Ahonen et al., Cancer Causes Control 11(2000) (847-852)) suggests that vitamin D deficiency may increase the risk of initiation and progression of prostate cancer. The nested case-control study was based on a 13-year follow-up of about 19000 middle-aged men free of clinically verified prostate cancer. More than one-half of the serum samples had 25OH-vitamin D (25-VD) levels below 50 nmol/l, suggesting VD deficiency. Prostate cancer risk was highest among the group of younger men (40-51 years) with low serum 25-VD, whereas low serum 25-VD appeared not to increase the risk of prostate cancer in older men (>51 years). This suggests that VD has a protective role against prostate cancer only before the andropause, when serum androgen concentrations are higher. The lowest 25-VD concentrations in the younger men were associated with more aggressive prostate cancer. Furthermore, the high 25-VD levels delayed the appearance of clinically verified prostate cancer by 1.8 years. Since these results suggest that vitamin D has a protective role against prostate cancer, we tried to determine whether full spectrum lighting (FSL) during working hours could increase serum 25-VD concentrations. After 1-month exposure, there was no significant increase in the serum 25-VD level, although there was a bias towards slightly increasing values in the test group as opposed to decreasing values in controls. There was no significant change in the skin urocanic acid production. The possibility to use FSL in cancer prevention is discussed. In order to clarify the mechanism of VD action on cell proliferation and differentiation, we performed studies with the rat and human prostates as well prostate cancer cell lines. It is possible that 25-VD may have a direct role in the host anticancer defence activity, but the metabolism of vitamin D in the prostate may also play an important role in its action. We raised antibodies against human 1alpha-hydroxylase and 24-hydroxylase. Our preliminary results suggest that vitamin D is actively metabolised in the prostate. Vitamin D appears to upregulate androgen receptor expression, whereas androgens seem to upregulate vitamin D receptor (VDR). This may at least partially explain the androgen dependence of VD action. VD alone or administered with androgen causes a suppression of epithelial cell proliferation. VD can activate mitogen-activated kinases, erk-1 and erk-2, within minutes and p38 within hours. Also, auto/paracrine regulation might be involved, since keratinocyte growth factor (mRNA and protein) was clearly induced by VD. Based on these studies, a putative model for VD action on cell proliferation and differentiation is presented.
J Steroid Biochem Mol Biol
PMID:Vitamin D and prostate cancer. 1138 70


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