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.

scholarly journals 1,25-dihydroxyvitamin-D3 but not the clinically applied marker 25-hydroxyvitamin-D3 predicts survival after stem cell transplantation

2020 ◽  
Author(s):  
Katrin Peter ◽  
Peter J. Siska ◽  
Tobias Roider ◽  
Carina Matos ◽  
Heiko Bruns ◽  
...  
Keyword(s):  
Vitamin D ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cox Model ◽  
Vitamin D Metabolites ◽  
Vitamin D Status ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
The Impact

Abstract The serum level of 25-hydroxyvitamin-D3 is accepted as marker for a person’s vitamin D status but its role for the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) is controversially discussed. The impact of 1,25-dihydroxyvitamin-D3 on HSCT outcome, however, has never been studied. In a discovery cohort of 143 HSCT patients we repeatedly (day −16 to 100) measured 1,25-dihydroxyvitamin-D3 and in comparison the well-established marker for serum vitamin D status 25-hydroxyvitamin-D3. Only lower 1,25-dihydroxyvitamin-D3 levels around HSCT (day −2 to 7, peritransplant) were significantly associated with higher 1-year treatment-related mortality (TRM) risk (Mann–Whitney U test, P = 0.001). This was confirmed by Cox-model regression without and with adjustment for baseline risk factors and severe acute Graft-versus-Host disease (aGvHD; unadjusted P = 0.001, adjusted P = 0.005). The optimal threshold for 1,25-dihydroxyvitamin-D3 to identify patients at high risk was 139.5 pM. Also in three replication cohorts consisting of altogether 365 patients 1,25-dihydroxyvitamin-D3 levels below 139.5 pM had a 3.3-fold increased risk of TRM independent of severe aGvHD compared to patients above 139.5 pM (Cox-model unadjusted P < 0.0005, adjusted P = 0.001). Our data highlight peritransplant 1,25-dihydroxyvitamin-D3 levels but not the commonly monitored 25-hydroxyvitamin-D3 levels as potent predictor of 1-year TRM and suggest to monitor both vitamin D metabolites in HSCT patients.

1,25-Dihydroxyvitamin D3-inducible catabolism of vitamin D metabolites in mouse intestine

1990 ◽  
Vol 258 (4) ◽  
pp. G557-G563 ◽  
Author(s):  
M. Tomon ◽  
H. S. Tenenhouse ◽  
G. Jones
Keyword(s):  
Vitamin D ◽  
Enzyme Activity ◽  
Actinomycin D ◽  
Vitamin D Metabolites ◽  
Catabolic Pathway ◽  
Dihydroxyvitamin D3 ◽  
Oxidation Pathway ◽  
1,25 Dihydroxyvitamin D3 ◽  
Mouse Intestine ◽  
Alpha Amanitin

The 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]-inducible C-24 oxidation pathway is a major catabolic pathway for vitamin D metabolites in target tissues. Using intestinal homogenates derived from 1,25(OH)2D3-treated mice, we examined the time course of induction, the intestinal localization and kinetics of induced enzyme activity, as well as the sensitivity of induction to transcriptional inhibitors actinomycin D and alpha-amanitin. 24-Hydroxylation of 500 nM 3H-labeled 25-hydroxyvitamin D3 [25(OH)D3] and 50 nM 3H-labeled 1,25(OH)2D3 by duodenal homogenates was detected 1 h after 1,25(OH)2D3 treatment; C-24 oxidation products of 25(OH)D3 and 1,25(OH)2D3 peaked at approximately 6 h and remained elevated for 17 h. Induced enzyme activity was localized to the mitochondrial fraction, was highest in duodenum, and was also detected in jejunum, ileum, and colon. The apparent Michaelis constant of the induced duodenal enzyme for 25(OH)D3 was 451 nM and for 1,25(OH)2D3 was 14 nM. Induction of intestinal catabolic activity was inhibited by prior treatment of 1,25(OH)2D3-injected mice with either actinomycin D or alpha-amanitin. The characteristics of the 1,25(OH)2D3-inducible C-24 oxidation pathway in the intestine resembled that of the kidney. However, the catabolic pathway was constitutively expressed only in the kidney. We conclude that 1,25(OH)2D3-inducible degradation of vitamin D metabolites occurs throughout the length of mouse intestine and can be prevented by transcriptional inhibitors, suggesting that mRNA synthesis is required for the induction process.

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.

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.

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.

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