scholarly journals Vitamin D metabolism and mechanisms of calcium transport.

1990 ◽  
Vol 1 (1) ◽  
pp. 30-42
Author(s):  
R Kumar
Keyword(s):  
Vitamin D ◽  
Calcium Binding ◽  
Active Form ◽  
Biologically Active ◽  
Vitamin D Metabolism ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
Magnesium Atpase ◽  
Liver And Kidney ◽  
Calcium Magnesium

Vitamin D3 undergoes sequential hydroxylations in the liver and kidney to form 1,25-dihydroxyvitamin D3, the biologically active form of the vitamin. 1,25-dihydroxyvitamin D3 is metabolized by several processes in various target tissues that decrease the biological activity of the sterol. In addition, 1,25-dihydroxyvitamin D3 is excreted in the bile as polar metabolites, such as glucuronides and, possibly sulfates and neutral polar steroids. These compounds undergo an enterohepatic recirculation in both man and experimental animals. 1,25-dihydroxyvitamin D3 increases the absorption of calcium in the intestine and the reabsorption of calcium in the kidney. It induces the synthesis of several proteins, the most notable of which is calcium binding protein that is thought to play a role in the absorption of calcium. The vitamin D-dependent calcium binding proteins and the calcium-magnesium ATPase calcium pump are co-localized in several tissues that play a role in the absorption of calcium.

Altered regulation of cytosolic Ca2+ concentration in dendritic cells from klotho hypomorphic mice

2013 ◽  
Vol 305 (1) ◽  
pp. C70-C77 ◽  
Author(s):  
Ekaterina Shumilina ◽  
Meerim K. Nurbaeva ◽  
Wenting Yang ◽  
Evi Schmid ◽  
Kalina Szteyn ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Vitamin D ◽  
Dendritic Cells ◽  
Active Form ◽  
Biologically Active ◽  
Deficient Diet ◽  
Dihydroxyvitamin D3 ◽  
Mhc Ii ◽  
Macrophage Colony ◽  
Antigen Presenting

The function of dendritic cells (DCs), antigen-presenting cells regulating naïve T-cells, is regulated by cytosolic Ca2+ concentration ([Ca2+]i). [Ca2+]i is increased by store-operated Ca2+ entry and decreased by K+-independent (NCX) and K+-dependent (NCKX) Na+/Ca2+ exchangers. NCKX exchangers are stimulated by immunosuppressive 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the biologically active form of vitamin D. Formation of 1,25(OH)2D3 is inhibited by the antiaging protein Klotho. Thus 1,25(OH)2D3 plasma levels are excessive in Klotho-deficient mice ( klotho hm). The present study explored whether Klotho deficiency modifies [Ca2+]i regulation in DCs. DCs were isolated from the bone marrow of klotho hm mice and wild-type mice ( klotho+/+) and cultured for 7–9 days with granulocyte-macrophage colony-stimulating factor. According to major histocompatibility complex II (MHC II) and CD86 expression, differentiation and lipopolysaccharide (LPS)-induced maturation were similar in klotho hm DCs and klotho+/+ DCs. However, NCKX1 membrane abundance and NCX/NCKX-activity were significantly enhanced in klotho hm DCs. The [Ca2+]i increase upon acute application of LPS (1 μg/ml) was significantly lower in klotho hm DCs than in klotho+/+ DCs, a difference reversed by the NCKX blocker 3′,4′-dichlorobenzamyl (DBZ; 10 μM). CCL21-dependent migration was significantly less in klotho hm DCs than in klotho+/+ DCs but could be restored by DBZ. NCKX activity was enhanced by pretreatment of klotho+/+ DC precursors with 1,25(OH)2D3 the first 2 days after isolation from bone marrow. Feeding klotho hm mice a vitamin D-deficient diet decreased NCKX activity, augmented LPS-induced increase of [Ca2+]i, and enhanced migration of klotho hm DCs, thus dissipating the differences between klotho hm DCs and klotho+/+ DCs. In conclusion, Klotho deficiency upregulates NCKX1 membrane abundance and Na+/Ca2+-exchange activity, thus blunting the increase of [Ca2+]i following LPS exposure and CCL21-mediated migration. The effects are in large part due to excessive 1,25(OH)2D3 formation.

scholarly journals Impact of Epigenetics on Complications of Fanconi Anemia: The Role of Vitamin D-Modulated Immunity

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1355
Author(s):  
Eunike Velleuer ◽  
Carsten Carlberg
Keyword(s):  
Vitamin D ◽  
Fanconi Anemia ◽  
Bone Marrow Failure ◽  
Active Form ◽  
Cellular Growth ◽  
Biologically Active ◽  
Fine Tuning ◽  
Dihydroxyvitamin D3 ◽  
Increased Risk ◽  
The Individual

Fanconi anemia (FA) is a rare disorder with the clinical characteristics of (i) specific malformations at birth, (ii) progressive bone marrow failure already during early childhood and (iii) dramatically increased risk of developing cancer in early age, such as acute myeloid leukemia and squamous cell carcinoma. Patients with FA show DNA fragility due to a defect in the DNA repair machinery based on predominately recessive mutations in 23 genes. Interestingly, patients originating from the same family and sharing an identical mutation, frequently show significant differences in their clinical presentation. This implies that epigenetics plays an important role in the manifestation of the disease. The biologically active form of vitamin D, 1α,25-dihydroxyvitamin D3 controls cellular growth, differentiation and apoptosis via the modulation of the immune system. The nuclear hormone activates the transcription factor vitamin D receptor that affects, via fine-tuning of the epigenome, the transcription of >1000 human genes. In this review, we discuss that changes in the epigenome, in particular in immune cells, may be central for the clinical manifestation of FA. These epigenetic changes can be modulated by vitamin D suggesting that the individual FA patient’s vitamin D status and responsiveness are of critical importance for disease progression.

Elevated 1,25-dihydroxyvitamin D3 and intestinal calbindin-D9k in the toothless rat

1990 ◽  
Vol 258 (2) ◽  
pp. E377-E381
Author(s):  
M. F. Seifert ◽  
R. W. Gray ◽  
M. E. Bruns
Keyword(s):  
Vitamin D ◽  
Calcium Binding ◽  
Morphological Evidence ◽  
Vitamin D Metabolites ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
Calbindin D9k ◽  
Plate Morphology ◽  
Circulating Levels ◽  
Phosphorus Levels

The toothless (tl) rat is a nonlethal osteopetrotic mutation characterized by systemic skeletal sclerosis, growth plate morphology suggestive of rickets, and morphological evidence of reduced osteoclastic bone resorption. Vitamin D metabolites, serum calcium and phosphorus levels, and the developmental appearance of vitamin D-dependent intestinal calcium binding protein (calbindin-D9k) was studied in normal and mutant rats of tl stock from 7 to 35 days of age. 1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] was found to be significantly elevated in mutant animals by 7 days of age (71 +/- 9 pM, tl/tl vs. 24 +/- 8 pM, +/?) and continued to increase to a peak of 428 pM at the time of weaning. This was 240% higher than normals at this period. The elevated levels of 1,25-(OH)2D3 stimulated a significant and precocious appearance of intestinal calbindin-D9k in mutants, beginning by 14 days of age and reaching their peak levels at 21 days postpartum (25.6 +/- 1.7 micrograms/mg protein, tl/tl vs. 16.4 +/- 1.5 micrograms/mg protein, +/?). The cause of the elevated circulating levels of 1,25-(OH)2D3 in tl rats is unknown but may be due to the low serum phosphorus levels present in these animals.

Duodenal and ileal calcium absorption in the rat and effects of vitamin D

1983 ◽  
Vol 244 (6) ◽  
pp. G695-G700 ◽  
Author(s):  
D. Pansu ◽  
C. Bellaton ◽  
C. Roche ◽  
F. Bronner
Keyword(s):  
Vitamin D ◽  
Calcium Binding ◽  
Calcium Transport ◽  
Calcium Absorption ◽  
Cytosolic Calcium ◽  
Chemical Gradient ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
Loop Procedure ◽  
Proximal Intestine

An in situ ligated loop procedure was applied to dissect transmural calcium transport in the intestine into two components, a saturable and a nonsaturable process. The existence of two such processes was confirmed in the duodenum, but ileal calcium transport was devoid of the saturable component. There was a small saturable component in the upper jejunum. The level of CaBP, the vitamin D-dependent cytosolic calcium-binding protein (Mr, approximately or equal to 9,000), corresponded to the magnitude of the saturable component. No CaBP was detected in the ileum. Vitamin D dependence of the saturable component was established by inducing it in the duodenum of vitamin D-deficient animals following intraperitoneal injection of 1,25-dihydroxyvitamin D3. In these same animals, conversely, the ileum did not respond to exogenous 1,25-dihydroxyvitamin D3. This confirms the absence in the ileum of the saturable component of transmural calcium movement and the fact that the nonsaturable component is not vitamin D dependent. Everted sac experiments also showed that duodenal sacs from vitamin D-replete or -repleted animals transported calcium against a chemical gradient, whereas ileal sacs did not. Vitamin D regulation of intestinal calcium absorption thus occurs only in the proximal intestine, even though calcium is absorbed down its chemical gradient all along the small intestine.

scholarly journals Cathelicidin, vitamin D3 dan imunitas terhadap tuberkulosis

2020 ◽  
Vol 20 (3) ◽  
Author(s):  
Yunita Arliny ◽  
Maryatun Hasan
Keyword(s):  
Vitamin D ◽  
Immune Response ◽  
Innate Immune Response ◽  
Vitamin D3 ◽  
Immune Cells ◽  
Active Form ◽  
Innate Immune ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
Natural Defense

Abstrak. Tuberkulosis (TB) merupakan salah satu penyakit infeksi yang menjadi masalah di dunia. Risiko untuk mendapatkan infeksi TB dipengaruhi oleh imunitas alamiah melawan mikobakteria. Peptida antimikroba merupakan salah satu barrier pertahanan alamiah. Cathelicidin adalah suatu peptida anti mikroba yang berperan pada proses imunitas terhadap TB. Cathelicidin Leusin Leusin-37 (LL-37) merupakan satu-satunya cathelicidin yang ada pada manusia dan dapat diekspresikan dari beberapa sel temasuk sel imun. Inducer Cathelicidin yang paling poten adalah 1,25-dihydroxyvitamin D3 yang merupakan bentuk aktif vitamin D 25(OH)D3. Tinjauan pustaka ini membahas tentang cathelicidin, vitamin D3 dam peranannya pada imunitas terhadap TB.Kata kunci: Cathelicidin, 1,25-dihydroxyvitamin D3, vitamin D 25(OH)2D3, imunitas, TuberkulosisAbstract. Tuberculosis is one of the most important infectious diseases worldwide. The susceptibility to this disease depends to great extent on the innate immune response against mycobacteria. Antimicrobial peptides are one of the natural defense barriers. Cathelicidin Leucine Leucine-37 (LL-37) is the only cathelicidin present in humans and synthesized by several cells including immune cells. The most effective inducer of Cathelicidin is 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3), which is an active form of vitamin D 25(OH)D3. This review discusses cathelicidin, vitamin D3 and its role in immunity against TBKeywords: Cathelicidin, 1,25-dihydroxyvitamin D3, vitamin D 25(OH)D3, immunity, Tuberkulosis

scholarly journals Assessment of Vitamin D Status in Male Osteoporosis

2006 ◽  
Vol 52 (2) ◽  
pp. 248-254 ◽  
Author(s):  
Ziad H Al-oanzi ◽  
Stephen P Tuck ◽  
Nicholas Raj ◽  
John S Harrop ◽  
Gregory D Summers ◽  
...  
Keyword(s):  
Vitamin D ◽  
Active Form ◽  
Biologically Active ◽  
Plasma Vitamin ◽  
Vitamin D Metabolites ◽  
Vitamin D Status ◽  
Total Plasma ◽  
Dihydroxyvitamin D3 ◽  
Idiopathic Osteoporosis ◽  
Free Vitamin D

Abstract Background: Clinical assessment of vitamin D status often relies on measuring total circulating 25-hydroxyvitamin D3 (25OHD3), but much of each vitamin D metabolite is bound to plasma vitamin D–binding protein (DBP), such that the percentage of free vitamin is very low. We hypothesized that measurement of free rather than total 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and 25OHD3 may provide better assessment of vitamin D status. We therefore aimed to assess vitamin D status in men with idiopathic osteoporosis, in whom possible secondary causes of osteoporosis had been excluded, and to determine the extent of change in biologically active “free” vitamin D caused by variation in plasma DBP concentrations. Methods: We measured 1,25(OH)2D3 and 25OHD3 in plasma samples from 56 men with idiopathic osteoporosis [mean (SD) age, 59.6 (13.6) years; range, 21–86 years] and 114 male controls [62.4 (10.4) years; range, 44–82 years]. Results: Mean total plasma 25OHD3 in the 56 men with osteoporosis and the 114 controls was 44.7 (21) and 43.3 (17) nmol/L, respectively; total plasma 1,25(OH)2D3 measured in randomly selected men with osteoporosis (n = 50) and controls (n = 50) was 90 (37) and 103 (39) pmol/L, respectively. Mean plasma DBP was significantly higher (P <0.001) in men with osteoporosis [224 (62) mg/L; n = 56] than in the controls [143 (34) mg/L; n = 114], but calculated free plasma 25OHD3 and 1,25(OH)2D3 were significantly lower in the osteoporotic men than in controls [6.1 (3.1) vs 9.1 (4.4) pmol/L (P <0.00001) and 77 (37) vs 142 (58) fmol/L (P <0.00001), respectively]. Conclusions: Measurement of total vitamin D metabolites alone, although providing a crude assessment of vitamin D status, may not give an accurate indication of the free (biologically active) form of the vitamin. The ratio of total 25OHD3 and 1,25(OH)2D3 to plasma DBP, rather than total circulating vitamin D metabolites, may provide a more useful index of biological activity. Further studies are required to substantiate this hypothesis.

Intestinal vitamin D-induced calcium-binding protein: time-course of immunocytological localization following 1,25-dihydroxyvitamin D3.

1983 ◽  
Vol 31 (3) ◽  
pp. 426-432 ◽  
Author(s):  
A N Taylor
Keyword(s):  
Vitamin D ◽  
Calcium Binding ◽  
Calcium Transport ◽  
Time Course ◽  
Binding Protein ◽  
Calcium Binding Protein ◽  
Dihydroxyvitamin D3 ◽  
Migration Rates ◽  
1,25 Dihydroxyvitamin D3 ◽  
Free Cells

The vitamin D-induced calcium-binding protein (CaBP) was localized in histological sections of chick duodenum using the peroxidase-antiperoxidase immunocytochemical technique. The time-course of appearance of CaBP in rachitic chicks was investigated from 0 to 120 hr after stimulation by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). CaBP was not routinely detected at 0 hr after 1,25(OH)2D3 administration. CaBP was first noted in some, but not all, of the samples taken 2 hr following 1,25(OH)2D3 and was detected in all 2 1/2 hr samples. The number of CaBP-containing absorptive cells and the apparent CaBP concentration both increased to a maximum at about 16-24 hr. At later times, as CaBP free cells migrated up the villi, the CaBP-containing cells decreased in number, but even at 120 hr post 1,25(OH)2D3 dose there were significant numbers of CaBP-containing cells present. The relationships between time-course of CaBP location on intestinal villi, enterocyte migration rates, and the time-course of 1,25(OH)2D3 stimulated intestinal calcium transport are discussed.

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