scholarly journals Uptake and degradation of filamentous actin and vitamin D-binding protein in the rat

1991 ◽  
Vol 274 (1) ◽  
pp. 237-241 ◽  
Author(s):  
S Dueland ◽  
M S Nenseter ◽  
C A Drevon
Keyword(s):  
Vitamin D ◽  
Binding Protein ◽  
Total Radioactivity ◽  
Liver Cells ◽  
Tissue Uptake ◽  
Rapid Rate ◽  
Vitamin D Binding Protein ◽  
Filamentous Actin ◽  
Parenchymal Liver

Tissue uptake and degradation of 125I-tyramine-cellobiose-labelled filamentous actin, vitamin D-binding protein (DBP) and actin-DBP complex were studied in the rat. Actin and actin-DBP complex were cleared from plasma at a faster rate than was DBP. About 40% of injected actin was recovered in the liver between 10 and 30 min after administration. Of the total radioactivity recovered in the liver, about 35% and 40% was detected in parenchymal and endothelial cells respectively when labelled actin or DBP-actin complex was injected intravenously. When labelled DBP alone was injected, approx. 55% of the radioactivity recovered in liver was in the Kupffer cells. These results suggest that actin is targeting the DBP-actin complex to the endothelial and parenchymal liver cells. Filamentous actin was also taken up in large amounts and at a rapid rate in parenchymal as well as non-parenchymal liver cells in vitro. Our data indicate that the rat has a mechanism to clear actin and the DBP-actin complex from plasma and that both parenchymal and non-parenchymal liver cells are involved in this process.

scholarly journals The effects of vitamin D binding protein-macrophage activating factor and colony-stimulating factor-1 on hematopoietic cells in normal and osteopetrotic rats

Blood ◽  
1996 ◽  
Vol 88 (8) ◽  
pp. 2898-2905 ◽  
Author(s):  
KA Benis ◽  
GB Schneider
Keyword(s):  
Bone Marrow ◽  
Vitamin D ◽  
Binding Protein ◽  
Bone Marrow Microenvironment ◽  
Colony Development ◽  
Colony Stimulating Factor ◽  
Vitamin D Binding Protein ◽  
Stimulating Factor

Osteopetrosis is a heterogeneous group of bone disorders characterized by the failure of osteoclasts to resorb bone and by several immunological defects including macrophage dysfunction. Two compounds, colony-stimulating factor-1 (CSF-1) and vitamin D-binding protein-macrophage activating factor (DBP-MAF) were used in the present study to evaluate their effects on the peritoneal population of cells and on cells within the bone marrow microenvironment in normal and incisors absent (ia) osteopetrotic rats. Previous studies in this laboratory have demonstrated that administration of DBP-MAF to newborn ia animals results in a substantial increase in bone marrow cavity size due to upregulated osteoclast function. To study the effects of these compounds on the macrophage/osteoclast precursors, DBP-MAF, CSF-1, and the combination of these compounds were given to newborn ia and normal littermate animals. Both the normal and mutant phenotypes responded similarly when treated with these compounds. Rats exhibited a profound shift toward the macrophage lineage from the neutrophil lineage when compared with vehicle-treated control animals after treatment with these compounds. In the in vivo peritoneal lavage study, animals received injections of CSF-1, DBP-MAF or DBP-MAF/CSF-1 over a 4-week period. The various types of cells in the peritoneal cavity were then enumerated. The in vitro study consisted of cells isolated from the bone marrow microenvironment and cultured on feeder layers of CSF-1, DBP-MAF, or DBP-MAF/CSF-1 for colony enumeration. The increase in macrophage numbers at the expense of neutrophil numbers could be seen in both the in vivo and in vitro experiments. The macrophage/osteoclast and neutrophil lineages have a common precursor, the granulocyte/macrophage colony-forming cell (GM-CFC). With the addition of CSF-1, the GM-CFC precursor may be induced into the macrophage/osteoclast lineage rather than the granulocyte lineage. This increased pool of cells in the macrophage/osteoclast lineage can be functionally upregulated with the subsequent addition of DBP-MAF to perform the activities of phagocytosis and bone resorption. The in vitro data also showed that DBP-MAF did not support colony development as in CSF-1 or the combination treatment. The recruitment and activation of cells into the macrophage/ osteoclast lineage may help to correct the bone and immune defects found in diseases demonstrating a significant lack of myeloid cells, as well as neutrophilia disorders and the disease, osteopetrosis.

scholarly journals Vitamin D-Binding Protein Influences Total Circulating Levels of 1,25-Dihydroxyvitamin D3 but Does Not Directly Modulate the Bioactive Levels of the Hormone in Vivo

Endocrinology ◽  
2008 ◽  
Vol 149 (7) ◽  
pp. 3656-3667 ◽  
Author(s):  
Lee A. Zella ◽  
Nirupama K. Shevde ◽  
Bruce W. Hollis ◽  
Nancy E. Cooke ◽  
J. Wesley Pike
Keyword(s):  
Vitamin D ◽  
Biological Activity ◽  
Binding Protein ◽  
Biologically Active ◽  
Vitamin D Binding Protein ◽  
Wild Type ◽  
Dihydroxyvitamin D3 ◽  
Activation Profile

Mice deficient in the expression of vitamin D-binding protein (DBP) are normocalcemic despite undetectable levels of circulating 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. We used this in vivo mouse model together with cells in culture to explore the impact of DBP on the biological activity of 1,25(OH)2D3. Modest changes in the basal expression of genes involved in 1,25(OH)2D3 metabolism and calcium homeostasis were observed in vivo; however, these changes seemed unlikely to explain the normal calcium balance seen in DBP-null mice. Further investigation revealed that despite the reduced blood levels of 1,25(OH)2D3 in these mice, tissue concentrations were equivalent to those measured in wild-type counterparts. Thus, the presence of DBP has limited impact on the extracellular pool of 1,25(OH)2D3 that is biologically active and that accumulates within target tissues. In cell culture, in contrast, the biological activity of 1,25(OH)2D3 is significantly impacted by DBP. Here, although DBP deficiency had no effect on the activation profile itself, the absence of DBP strongly reduced the concentration of exogenous 1,25(OH)2D3 necessary for transactivation. Surprisingly, analogous studies in wild-type and DBP-null mice, wherein we explored the activity of exogenous 1,25(OH)2D3, produced strikingly different results as compared with those in vitro. Here, the carrier protein had virtually no impact on the distribution, uptake, activation profile, or biological potency of the hormone. Collectively, these experiments suggest that whereas DBP is important to total circulating 1,25(OH)2D3 and sequesters extracellular levels of this hormone both in vivo and in vitro, the binding protein does not influence the hormone’s biologically active pool.

Vitamin D analogs with low affinity for the vitamin D binding protein: Enhanced in vitro and decreased in vivo activity

2009 ◽  
Vol 6 (10) ◽  
pp. 1051-1057 ◽  
Author(s):  
Roger Bouillon ◽  
Katrien Allewaert ◽  
Da Zhen Xiang ◽  
Biauw Keng Tan ◽  
Hugo van Baelen
Keyword(s):  
Vitamin D ◽  
Binding Protein ◽  
Vitamin D Binding Protein ◽  
Vitamin D Analogs

scholarly journals Uptake and degradation of vitamin D binding protein and vitamin D binding protein–actin complex in vivo in the rat

1990 ◽  
Vol 267 (3) ◽  
pp. 721-725 ◽  
Author(s):  
S Dueland ◽  
R Blomhoff ◽  
J I Pedersen
Keyword(s):  
Vitamin D ◽  
Intravenous Injection ◽  
Binding Protein ◽  
Tissue Uptake ◽  
Vitamin D Binding Protein ◽  
Labelling Technique ◽  
Labelling Method

We have labelled the rat vitamin D binding protein (DBP), DBP-actin and rat albumin with 125I-tyramine-cellobiose (125I-TC). In contrast with traditional 125I-labelling techniques where degraded radioactive metabolites are released into plasma, the 125I-TC moiety is trapped intracellularly in the tissues, where the degradation of the labelled proteins takes place. By using this labelling method, the catabolism of proteins can be studied in vivo. In this study we have used this labelling technique to compare the tissue uptake and degradation of DBP, DBP-actin and albumin in the rat. DBP-actin was cleared from plasma at a considerably faster rate than DBP. After intravenous injection of labelled DBP-actin complex, 48% of the radioactive dose was recovered in the liver after 30 min, compared with 14% when labelled DBP was administered. Only small amounts of DBP-actin complex were recovered in the kidneys. In contrast with the results obtained with DBP-actin complex, liver and kidneys contributed about equally in the uptake and degradation of DBP determined 24 h after the injection. When labelled DBP was compared with labelled albumin, the amount of radioactivity taken up by the liver and kidneys by 24 h after the injection was 2 and 5 times higher respectively. In conclusion, liver and kidneys are the major organs for catabolism of DBP in the rat. Furthermore, binding of actin to DBP enhances the clearance of DBP from circulation as well as its uptake by the liver.

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