scholarly journals L-cysteine supplementation upregulates glutathione (GSH) and vitamin D binding protein (VDBP) in hepatocytes cultured in high glucose and in vivo in liver, and increases blood levels of GSH, VDBP, and 25-hydroxy-vitamin D in Zucker diabetic fatty rats

2016 ◽  
Vol 60 (5) ◽  
pp. 1090-1098 ◽  
Author(s):  
Sushil K. Jain ◽  
Preeti Kanikarla-Marie ◽  
Cassandra Warden ◽  
David Micinski
Keyword(s):  
Vitamin D ◽  
High Glucose ◽  
Binding Protein ◽  
Blood Levels ◽  
Vitamin D Binding Protein ◽  
Zucker Diabetic Fatty Rats ◽  
25 Hydroxy Vitamin D

Vitamin D homeostasis is compromised due to increased urinary excretion of the 25-hydroxycholecalciferol-vitamin D-binding protein complex in the Zucker diabetic fatty rat

2010 ◽  
Vol 299 (6) ◽  
pp. E959-E967 ◽  
Author(s):  
R. L. Anderson ◽  
S. B. Ternes ◽  
K. A. Strand ◽  
M. J. Rowling
Keyword(s):  
Vitamin D ◽  
Urinary Excretion ◽  
Binding Protein ◽  
Serum Vitamin ◽  
Vitamin D Status ◽  
Vitamin D Binding Protein ◽  
Renal Reabsorption ◽  
Vitamin D Levels ◽  
Zucker Diabetic Fatty Rats ◽  
25 Hydroxycholecalciferol

Altered serum concentrations of the major circulating form of vitamin D [25-hydroxycholecalciferol (25D3)] and its active hormone derivative [1,25-dihydroxycholecalciferol (1,25D3)] have been linked to non-insulin-dependent diabetes mellitus (NIDDM). However, a mechanistic basis for this occurrence has not been fully elucidated. Normally, renal reabsorption of vitamin D-binding protein-bound 25D3 absolutely requires receptor-mediated endocytosis via a receptor complex containing megalin, cubilin, and disabled-2 (Dab2), whereas an absence of megalin or its endocytic partners can lead to a marked urinary loss of 25D and severe vitamin D deficiency. Therefore, we hypothesized that reduced serum vitamin D status in NIDDM may be due to reduced expression of megalin and/or its endocytic partners and increased urinary excretion of protein-complexed 25D3. In the present study, we utilized Zucker diabetic fatty Rats (ZDF) to demonstrate that renal reuptake of the 25D3-DBP complex was compromised in ZDF animals, which was reflected by a reduction in expression of megalin and Dab2. Moreover, serum levels of both 25D3 and 1,25D3 were reduced, and urinary 25D3, 1,25D3, and DBP excretion were elevated in the ZDF animals compared with their lean controls regardless of vitamin D levels in the diet. Taken together, these are the first reports to our knowledge that associate compromised renal reabsorption of the 25D3-DBP complex with expression of megalin and its endocytic partners in NIDDM, which in turn can lead to compromised vitamin D status.

scholarly journals An Intronic Locus Control Region Plays an Essential Role in the Establishment of an Autonomous Hepatic Chromatin Domain for the Human Vitamin D-Binding Protein Gene

2007 ◽  
Vol 27 (21) ◽  
pp. 7365-7380 ◽  
Author(s):  
Tomoko Hiroki ◽  
Stephen A. Liebhaber ◽  
Nancy E. Cooke
Keyword(s):  
Vitamin D ◽  
Copy Number ◽  
Binding Protein ◽  
Critical Role ◽  
Chromatin Domain ◽  
Dependent Manner ◽  
Vitamin D Binding Protein ◽  
Intron 1 ◽  
Factor C

ABSTRACT The human vitamin D-binding protein (hDBP) gene exists in a cluster of four liver-expressed genes. A minimal hDBP transgene, containing a defined set of liver-specific DNase I hypersensitive sites (HSs), is robustly expressed in mouse liver in a copy-number-dependent manner. Here we evaluate these HSs for function. Deletion of HSI, located 5′ to the promoter (kb −2.1) had no significant effect on hDBP expression. In contrast, deletion of HSIV and HSV from intron 1 repressed hDBP expression and eliminated copy number dependency without a loss of liver specificity. Chromatin immunoprecipitation analysis revealed peaks of histone H3 and H4 acetylation coincident with HSIV in the intact hDBP locus. This region contains a conserved array of binding sites for the liver-enriched transcription factor C/EBP. In vitro studies revealed selective binding of C/EBPα to HSIV. In vivo occupancy of C/EBPα at HSIV was demonstrated in hepatic chromatin, and depletion of C/EBPα in a hepatic cell line decreased hDBP expression. A nonredundant role for C/EBPα was confirmed in vivo by demonstrating a reduction of hDBP expression in C/EBPα-null mice. Parallel studies revealed in vivo occupancy of the liver-enriched factor HNF1α at HSIII (at kb 0.13) within the hDBP promoter. These data demonstrate a critical role for elements within intron 1 in the establishment of an autonomous and productive hDBP chromatin locus and suggest that this function is dependent upon C/EBPα. Cooperative interactions between these intronic complexes and liver-restricted complexes within the target promoter are likely to underlie the consistency and liver specificity of the hDBP activation.

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

Influence of obesity on vitamin D–binding protein and 25-hydroxy vitamin D levels in African American and white women

Metabolism ◽  
2009 ◽  
Vol 58 (4) ◽  
pp. 438-442 ◽  
Author(s):  
Stephen J. Winters ◽  
Ramana Chennubhatla ◽  
Chenxi Wang ◽  
James J. Miller
Keyword(s):  
Vitamin D ◽  
African American ◽  
White Women ◽  
Binding Protein ◽  
Vitamin D Binding Protein ◽  
Vitamin D Levels ◽  
25 Hydroxy Vitamin D

No association of vitamin D binding protein gene polymorphisms with ulcerative colitis in Chinese patients

2019 ◽  
Author(s):  
Fubin Qiu ◽  
Lijuan Zhang ◽  
Jing Wang ◽  
Rui Li ◽  
Linxue Yang
Keyword(s):  
Ulcerative Colitis ◽  
Vitamin D ◽  
Binding Protein ◽  
Case Control ◽  
Chinese Patients ◽  
Vitamin D Binding Protein ◽  
Chinese Han ◽  
Gene Encoding ◽  
Significant Difference

Abstract Object Vitamin D (VD) deficiency has been reported in patients with ulcerative colitis (UC), and polymorphism in the gene encoding the vitamin D binding protein (DBP) can affect the characteristics of DBP, thus affecting the level and function of VD in vivo . Previous studies have rarely reported on the potential relationship between DBP polymorphisms and UC. To investigate the associations between genetic variants in DBP genes and UC susceptibility in the Han Chinese population, in order to discern whether any differences exist between this population and those of other countries.Methods In this case-control study, the genotyping of DBP rs4588 and rs7041 polymorphisms was conducted using polymerase chain reaction (PCR)-ligase detection reactions, and the rs4588 and rs7041 genotypes were detected by PCR-restriction fragment length polymorphism.Results In our case-control cohort, no significant difference was observed in the UC risk for either of the two SNPs (rs4588 and rs7401) in the DBP genes ( P > 0.05). No association between UC susceptibility and the DBP gene haplotypes was found either.Conclusions Our results suggest that the two SNPs (rs4588 and rs7401) in the DBP genes may have no correlation with susceptibility to UC in the Chinese Han population. But interestingly, haplotype GC, which contains the rs4588 and rs7041 variants in the DBP gene, may affect the level of oxidative stress in UC patients, especially the level of MDA.

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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