scholarly journals Target cell metabolism of 1,25-dihydroxyvitamin D3 to calcitroic acid. Evidence for a pathway in kidney and bone involving 24-oxidation

1989 ◽  
Vol 262 (1) ◽  
pp. 173-180 ◽  
Author(s):  
G Makin ◽  
D Lohnes ◽  
V Byford ◽  
R Ray ◽  
G Jones
Keyword(s):  
Bone Cells ◽  
Cell Metabolism ◽  
Osteoblastic Cell ◽  
Target Cells ◽  
Dihydroxyvitamin D3 ◽  
Osteoblastic Cell Line ◽  
Oxidation Pathway ◽  
1,25 Dihydroxyvitamin D3 ◽  
Rapid Clearance ◽  
Umr 106

1,25-dihydroxyvitamin D3 is converted to calcitroic acid before being excreted in the bile. Biosynthesis of calcitroic acid has been demonstrated in two target cells of vitamin D, in the kidney and the osteoblastic cell line UMR-106. Calcitroic acid was identified by combinations of h.p.l.c., u.v. spectroscopy and mass spectrometry. Evidence is presented that calcitroate is derived from the 24-oxidation pathway, possibly through the intermediate 24,25,26,27-tetranor-1,23-dihydroxyvitamin D3. The 24-oxidation pathway to calcitroic acid in bone cells is stimulated by 1,25-dihydroxyvitamin D3. The pathway in both bone cells and perfused kidney operates at physiological concentrations of substrate and appears to be capable of rapid clearance of the hormone.

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.

scholarly journals 1,25-dihydroxyvitamin D3 differentiates normal neutrophilic promyelocytes to monocytes/macrophages in vitro

Blood ◽  
1996 ◽  
Vol 87 (7) ◽  
pp. 2693-2701 ◽  
Author(s):  
K Nakamura ◽  
T Takahashi ◽  
Y Sasaki ◽  
R Tsuyuoka ◽  
Y Okuno ◽  
...  
Keyword(s):  
Target Cells ◽  
Essential Factor ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
Morphological Evaluation ◽  
Secondary Culture ◽  
Normal Human ◽  
The Individual ◽  
Stimulating Factor

Although it is well established that the addition of 1,25- dihydroxyvitamin D3 (D3) to the culture of normal human granulocyte/macrophage progenitors induces monocyte/macrophage (Mo/M phi) colonies, the target cells of D3 in the Mo/M phi differentiation have not been identified. We examined whether neutrophilic promyelocytes are the target cells. As a source of the promyelocyte fraction, we used colonies after 5 days of culture (5-day colonies) of colony-forming unit-granulocyte. The culture contained granulocyte colony-stimulating factor (G-CSF) as the growth factor and generated only neutrophilic colonies. The promyelocytic nature of the 5-day colonies was confirmed morphologically, cytochemically, and ultrastructurally. After morphological evaluation on part of the individual colonies, they were transferred into new semisolid cultures with or without D3 (10(-7) mol/L) in the presence of G-CSF, then incubated for the subsequent 7 days. With D3, the colonies were loose, and all the constituent cells were morphologically small macrophages, which were positive for alpha-naphthyl butyrate (alpha NB) esterase, strongly positive for CD14 antigen, and plastic-adherent. While without D3, the colonies were rather compact, and all the constituent cells were morphologically mature neutrophils, which were positive for naphthol ASD-chloroacetate esterase and weakly positive for CD14 antigen. Secondary culture of the 8- or 10-day colonies with D3 induced a lower number of alpha NB-positive cells, in proportion to the percentage of promyelocytes at the time of transfer in each colony. Four days of secondary culture with D3 was sufficient to induce alpha NB-positive cells. G-CSF was not an essential factor to induce alpha NB- positive cells. These findings indicate that D3 differentiates normal human neutrophilic promyelocytes into the Mo/M phi lineage in vitro.

Effect of natural uranium on the UMR-106 osteoblastic cell line: impairment of the autophagic process as an underlying mechanism of uranium toxicity

2016 ◽  
Vol 91 (4) ◽  
pp. 1903-1914 ◽  
Author(s):  
Valérie Pierrefite-Carle ◽  
Sabine Santucci-Darmanin ◽  
Véronique Breuil ◽  
Tatiana Gritsaenko ◽  
Claude Vidaud ◽  
...  
Keyword(s):  
Cell Line ◽  
Underlying Mechanism ◽  
Natural Uranium ◽  
Osteoblastic Cell ◽  
Osteoblastic Cell Line ◽  
Uranium Toxicity ◽  
Autophagic Process ◽  
Umr 106
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