New Vitamin D Metabolite localized in Intestinal Cell Nuclei

Nature ◽  
1969 ◽  
Vol 222 (5189) ◽  
pp. 171-172 ◽  
Author(s):  
D. E. M. LAWSON ◽  
P. W. WILSON ◽  
E. KODICEK
Keyword(s):  
Vitamin D ◽  
Intestinal Cell ◽  
Cell Nuclei

scholarly journals The localization of 1,25-dihydroxycholecalciferol in bone cell nuclei of rachitic chicks

1971 ◽  
Vol 125 (1) ◽  
pp. 147-153 ◽  
Author(s):  
J. C. Weber ◽  
V. Pons ◽  
E. Kodicek
Keyword(s):  
Vitamin D ◽  
Subcellular Distribution ◽  
Time Course ◽  
Supernatant Fraction ◽  
Intestinal Cell ◽  
Nuclear Fraction ◽  
Vitamin D Metabolites ◽  
Cell Nuclei ◽  
Polar Metabolite ◽  
25 Hydroxycholecalciferol

1. A simple technique has been developed to obtain subcellular fractions of chick bone. The method yielded 60–70% of total DNA in the nuclear debris fraction and 80–90% of total 14C recovered in bone after a dose of radioactive vitamin D. 2. After a dose of [4-14C,1,2-3H2]cholecalciferol (0.5μg) was given to vitamin D-deficient chicks, the time-course of total 14C radioactivity in the epiphysis, metaphysis and diaphysis of proximal tibiae was measured. The maximum concentrations were reached at 6h, corresponding to a similar peak of radioactivity in blood, decreasing until 24h and indicating the dependence on the circulating 14C and on the blood supply of the three bone components. 3. The 14C radioactivity of cholecalciferol and 25-hydroxycholecalciferol (expressed per mg of DNA) followed the pattern of incorporation of total 14C radioactivity in all three bone components. The more polar metabolite fraction reached a peak of radioactivity at 6–9h and maintained its concentration over the 24h period studied in all anatomical bone components. 4. After a dose of [4-14C,1-3H]cholecalciferol (0.5μg) was given to vitamin D-deficient chicks, the subcellular distribution was studied. At 24h after dosing, the nuclear fraction contained 27% and the supernatant fraction had 67% of total 14C recovered in the bone filtrate. When the 14C in the residual bone fragments was included, the nuclear fraction contained up to 35% of the total radioactivity in the bone. 5. The subcellular distribution pattern of individual vitamin D metabolites indicated that the purified nuclear fraction concentrated the polar metabolite, which lost 3H at C-1, so that 77% of the radioactivity could be accounted for by 1,25-dihydroxycholecalciferol. The supernatant fraction contained smaller amounts of 1,25-dihydroxycholecalciferol (9%), with 66% of 25-hydroxycholecalciferol forming the major metabolite, corresponding to its concentration found in blood at 24h. 6. The preferential accumulation of 1,25-dihydroxycholecalciferol in the nuclear fraction and the overall pattern of other metabolites, found previously in intestinal tissue, suggests a similar mechanism of action in bone to that postulated for the intestinal cell in calcium translocation.

Vitamin D-regulated calcium transport in Caco-2 cells: unique in vitro model

1991 ◽  
Vol 260 (2) ◽  
pp. G207-G212 ◽  
Author(s):  
A. R. Giuliano ◽  
R. J. Wood
Keyword(s):  
Vitamin D ◽  
Cell Line ◽  
Calcium Transport ◽  
In Vitro Model ◽  
Colon Adenocarcinoma ◽  
Intestinal Cell ◽  
Maximal Velocity ◽  
Dependent Manner ◽  
Vitro Model

The human colon adenocarcinoma cell line Caco-2 is the only intestinal cell line to differentiate spontaneously in culture exhibiting structural and biochemical characteristics of mature enterocytes and to possess a vitamin D receptor in the fully differentiated state. Transepithelial calcium transport was characterized in differentiated Caco-2 cells grown on permeable filters supports to assess the potential utility of this cell line as an in vitro model to study 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]-induced calcium transport. Calcium transport was increased in a dose-dependent manner by 1,25(OH)2D3. Total calcium transport at different calcium concentrations could be fitted to a modified Michaelis-Menten equation containing a linear transport component. The maximum rate of saturable calcium transport was increased by 4.3-fold (P less than 0.005) in cells treated with 10(-8) M 1,25(OH)2D3. This treatment also increased the apparent buffer calcium concentration that results in half-maximal velocity from 0.4 to 1.3 mM but had no significant effect on nonsaturable calcium transport. Caco-2 cells grown on permeable filter supports provide a unique in vitro human cell culture model to study the mechanism of vitamin D-regulated transepithelial intestinal calcium transport.

The Role of Vitamin D in Bone and Intestinal Cell Differentiation

1990 ◽  
Vol 10 (1) ◽  
pp. 195-211 ◽  
Author(s):  
T Suda ◽  
T Shinki ◽  
N Takahashi
Keyword(s):  
Vitamin D ◽  
Cell Differentiation ◽  
Intestinal Cell

scholarly journals Vitamin D–vitamin D receptor system down-regulates expression of uncoupling proteins in brown adipocyte through interaction with Hairless protein

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Pei-qi Wang ◽  
Dao-xiang Pan ◽  
Chun-qiu Hu ◽  
Yu-lin Zhu ◽  
Xiao-jing Liu
Keyword(s):  
Vitamin D ◽  
Adipose Tissue ◽  
Vitamin D Deficiency ◽  
Vitamin D Receptor ◽  
Brown Adipocyte ◽  
Dependent Manner ◽  
Cell Nuclei ◽  
Down Regulation ◽  
Brown Adipocytes ◽  
Brown Adipose

Abstract Our previous study showed that feeding mice with vitamin D deficiency diet markedly alleviated high-fat-diet-induced overweight, hyperinsulinemia, and hepatic lipid accumulation. Moreover, vitamin D deficiency up-regulated the expression of uncoupling protein 3 (Ucp3) in white adipose tissue (WAT) and brown adipose tissue (BAT). The present study aimed to further investigate the effects of vitamin D and vitamin D receptor (Vdr) on Ucp1–3 (Ucps) expression in brown adipocyte and the mechanism involved in it. Rat primary brown adipocytes were separated and purified. The effects of the 1,25(OH)2D3 (1,25-dihydroxyvitamin D3; the hormonal form of vitamin D) and Vdr system on Ucps expression in brown adipocytes were investigated in basal condition and activated condition by isoproterenol (ISO) and triiodothyronine (T3). Ucps expression levels were significantly down-regulated by 1,25(OH)2D3 in the activated brown adipocyte. Vdr silencing reversed the down-regulation of Ucps by 1,25(OH)2D3, whereas Vdr overexpression strengthened the down-regulation effects. Hairless protein did express in brown adipocyte and was localized in cell nuclei. 1,25(OH)2D3 increased Hairless protein expression in the cell nuclei. Hairless (Hr) silencing notably elevated Ucps expression in activated condition induced by ISO and T3. Moreover, immunoprecipitation results revealed that Vdr could interact with Hairless, which might contribute to decreasing expression of Vdr target gene Ucps. These data suggest that vitamin D suppresses expression of Ucps in brown adipocyte in a Vdr-dependent manner and the corepressor Hairless protein probably plays a role in the down-regulation.

scholarly journals The response of the small intestine to vitamin D. Correlation between calcium-binding-protein production and increased calcium absorption

1974 ◽  
Vol 144 (2) ◽  
pp. 339-346 ◽  
Author(s):  
J S Emtage ◽  
D E M Lawson ◽  
E Kodicek
Keyword(s):  
Vitamin D ◽  
Protein Synthesis ◽  
Small Intestine ◽  
Calcium Binding ◽  
Protein Production ◽  
Calcium Absorption ◽  
Binding Protein ◽  
Calcium Binding Protein ◽  
Intestinal Cell ◽  
Stimulation Of

1. The synthesis of calcium-binding protein, a protein produced in the small intestine in response to vitamin D, was investigated with a view to determining whether calcium-binding-protein production could be correlated with the stimulation of calcium absorption by vitamin D. 2. A radioimmunological assay, which can quantitatively estimate calcium-binding-protein concentrations as low as 1μg/g wet wt., was used to detect the synthesis of soluble calcium-binding protein. 3. When used on intestinal supernatants from chicks dosed with vitamin D, calcium-binding protein was not detectable at 8h but was present after 12h at a concentration of 8.6μg/g wet wt.; in agreement with this an increase in calcium absorption due to vitamin D was detected at 12h but not at 8h. 4. The synthesis of calcium-binding protein was also monitored directly by making use of the ability of the iodinated antiserum to bind specifically to nascent calcium-binding protein chains on intestinal polyribosomes; in this way calcium-binding-protein synthesis could be detected 8h after dosage with vitamin D. Further, the binding reaction indicated a near linear increase in the calcium-binding-protein-synthesizing capacity over a 16h period. 5. From the amount of calcium-binding protein present 12 and 24h after vitamin D administration it is calculated that calcium-binding-protein mRNA is produced at approx. 1mol/min per intestinal cell. 6. It is concluded that the high correlation between the initiation of calcium-binding-protein synthesis and the stimulation of calcium absorption by vitamin D strengthens the proposal that calcium-binding protein plays an important role in calcium transport.

scholarly journals Vitamin D3 suppresses intestinal epithelial stemness via ER stress induction in intestinal organoids

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Panida Sittipo ◽  
Hyun Kyu Kim ◽  
Jaeseok Han ◽  
Man Ryul Lee ◽  
Yun Kyung Lee
Keyword(s):  
Vitamin D ◽  
Cell Death ◽  
Er Stress ◽  
Fluorescent Protein ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Intestinal Cell ◽  
Intestinal Epithelial ◽  
Expression Levels ◽  
Intestinal Organoids

Abstract Background Vitamin D3 is important for normal function of the intestinal epithelial cells (IECs). In this study, we aimed to investigate the effects of vitamin D3 on the differentiation, stemness, and viability of healthy IECs in intestinal organoids. Methods Intestinal organoids derived from mouse small intestine were treated with vitamin D3, and the effects on intestinal stemness and differentiation were evaluated using real-time PCR and immunofluorescence staining of the distinct lineage markers. Cell viability was analyzed using viability and apoptosis assays. Results Vitamin D3 enhanced IEC differentiation into the distinct lineages of specialized IECs, including Paneth, goblet, and enteroendocrine cells and absorptive enterocytes. Decreased expression levels of leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) and the presence of several LGR5-green fluorescent protein (GFP)-positive cells were observed in vitamin D3-treated organoids derived from LGR5-GFP mice. The formation of the crypt-villus structure was also inhibited by vitamin D3, suggesting that vitamin D3 suppresses intestinal cell stemness. Furthermore, the expression levels of unfolded protein response genes, C/EBP homologous protein (CHOP), and activating transcription factor 6 (ATF6) were upregulated in vitamin D3-treated organoids. Moreover, vitamin D3 promoted apoptotic cell death in intestinal cells, which may be associated with the decrease in intestinal stemness. LGR5 gene expression, ISC number, and apoptotic cell death were partially recovered in the presence of the ER stress inhibitor tauroursodeoxycholic acid (TUDCA), suggesting that intestinal stemness suppression and intestinal apoptosis occurred via ER stress activation. Conclusions Our study provides important insights into the effects of vitamin D3 on the induction of IEC differentiation and apoptotic cell death, and inhibition of intestinal stemness accompanied by ER stress augmentation.

scholarly journals Intestinal cell-specific vitamin D receptor (VDR)-mediated transcriptional regulation of CYP3A4 gene

2010 ◽  
Vol 79 (2) ◽  
pp. 277-287 ◽  
Author(s):  
Petr Pavek ◽  
Katerina Pospechova ◽  
Lucie Svecova ◽  
Zdenka Syrova ◽  
Lucie Stejskalova ◽  
...  
Keyword(s):  
Vitamin D ◽  
Transcriptional Regulation ◽  
Vitamin D Receptor ◽  
Intestinal Cell ◽  
Cyp3a4 Gene

scholarly journals The response of the small intestine to vitamin D. Isolation and properties of chick intestinal polyribosomes

1974 ◽  
Vol 140 (2) ◽  
pp. 239-247 ◽  
Author(s):  
J. Spencer Emtage ◽  
D. Eric M. Lawson ◽  
Egon Kodicek
Keyword(s):  
Vitamin D ◽  
Small Intestine ◽  
Rat Liver ◽  
Liver Cell ◽  
Calcium Binding ◽  
De Novo ◽  
Binding Protein ◽  
Calcium Binding Protein ◽  
Intestinal Cell ◽  
Polypeptide Chains

Undegraded polyribosome preparations may be obtained from chick intestinal mucosa if ribonuclease activity is strictly controlled. This is best achieved by homogenization of the mucosa directly in rat liver cell-sap. 2. The extent of amino acid incorporation by chick intestinal polyribosomes is greatly influenced by the source of the cell-sap. Sephadex-treated intestinal cell-sap caused impaired incorporation and release of completed polypeptide chains, whereas Sephadex-treated rat liver cell-sap promoted the polymerization of up to 90 amino acids per ribosome. Under optimum conditions 30–35% of the nascent polypeptide chains are completed and released. 3. The preparation of an antiserum against the calcium-binding protein formed in response to vitamin D is described. It is shown that the antiserum is highly specific for calcium-binding protein. 4. This antiserum was used to investigate the ability of chick intestinal polyribosomes to synthesize calciumbinding protein. Only polyribosomes from chicks receiving vitamin D have the ability to synthesize calcium-binding protein. Moreover, the product formed in vitro has the same electrophoretic mobility as calcium-binding protein synthesized in vivo. 5. It is concluded that one of the main functions of vitamin D in the small intestine is to induce the synthesis de novo of calcium-binding protein.

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