The glycosylation and characterization of the candidate Gc macrophage activating factor

Ravnsborg, Tina; Olsen, Dorthe T.; Thysen, Anna Hammerich; Christiansen, M.; Højrup, Peter

doi:10.1016/j.bbapap.2009.12.022

Cited by 29 publications

(22 citation statements)

References 60 publications

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“…Several studies and clinical trials have published extraordinary biological activities in the treatment of patients with breast-, colorectal-and prostate cancer as well as HIV [3]. However recently, the reports regarding immunotherapy with DBP-MAF have been retracted due to irregularities in the documentation for institutional review board approval [118].…”

Section: The Influence Of Vitamin D Binding Protein On T Cell Responsementioning

confidence: 97%

“…DBP1F and DBP1S have an identical primary structure, except at position 416, where aspartic acid is substituted by glutamic acid. The partial glycosylation of DBP1S comprises a linear O-linked trisaccharide of the type GalNAc-Gal-Sia attached to the threonine residue at position 420 [3,9]. Besides the three common alleles, a large number (>120) of unique racial variants [10] and single nucleotide polymorphisms (SNPs) of DBP have been described [11].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Behind the scenes of vitamin D binding protein: More than vitamin D binding

Delanghe

Speeckaert

2015

Best Practice & Research Clinical Endocrinology & Metab

139

122

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Section: The Influence Of Vitamin D Binding Protein On T Cell Responsementioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Behind the scenes of vitamin D binding protein: More than vitamin D binding

Delanghe

Speeckaert

2015

Best Practice & Research Clinical Endocrinology & Metab

139

122

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“…GC-1f is a combination of aspartic acid at position 432 and threonine at 436; GC-1s has a combination of glutamic acid at position 432 and threonine at 436, and GC-2 has a combination of aspartic acid at position 432 and lysine at 436 [9,10,11]. Previous research indicates that these differences in amino acid sequence are associated with variations in DBP affinity for 25(OH)D, with GC-1f having the highest, GC-1s having intermediate and GC-2 having the lowest affinity for 25(OH)D [10,11,27,28]. However, the biologic importance of binding affinity is uncertain, since only small quantities of 25(OH)D appear as unbound hormone.…”

Section: Discussionmentioning

confidence: 99%

“…The three major isoforms of DBP are distinguished by their amino acid composition and glycosylation patterns [26,27]. GC-1f is a combination of aspartic acid at position 432 and threonine at 436; GC-1s has a combination of glutamic acid at position 432 and threonine at 436, and GC-2 has a combination of aspartic acid at position 432 and lysine at 436 [9,10,11].…”

Section: Discussionmentioning

confidence: 99%

Variations in the Vitamin D-Binding Protein (DBP) Gene Are Related to Lower 25-Hydroxyvitamin D Levels in Healthy Girls: A Cross-Sectional Study

Santos¹,

Mascarenhas²,

Boguszewski³

et al. 2013

Horm Res Paediatr

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Background/Aims: Vitamin D deficiency has been recognized as a worldwide epidemic affecting several pediatric and adolescent populations. We determined the genotype and haplotype distribution of the rs4588 and rs7041 polymorphisms of the GC gene encoding vitamin D-binding protein (DBP)and investigated the associations between these gene variants and their haplotypes with 25-hydroxyvitamin D [25(OH)D] levels in girls from South Brazil. Methods: Cross-sectional study including 198 apparently healthy girls aged 10-18 years. Plasma levels of 25(OH)D were assessed by radioimmunoassay. Participants were genotyped for rs4588 and rs7041 by real-time PCR, with allelic discrimination assays. Results: Mean chronological age and BMI percentile were 13.17 ± 1.74 years and 57.81 ± 29.03, respectively. Sufficient circulating 25(OH)D levels (≥30 ng/ml) were found in 9.1% of the overall group, insufficient levels (20-29.9 ng/ml) in 59.6%, and deficient levels (<20 ng/ml) in 31.3%. The AA genotype of rs4588, TT genotype of rs7041 and CT-AT/AT-AT (GC 1f-2/2-2) diplotypes were significantly associated with lower 25(OH)D levels, even after adjustment for age and season at the time of blood collection. Conclusions: The GC gene genotype may be related to the susceptibility to low 25(OH)D levels in female children and adolescents.

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“…DBP exists in different isoforms and the one designated Gc1s is glycosylated and comprises a linear O-linked trisaccharide of the type GalNAcGal-Sia attached to the threonine residue at position 420 [7]. During immune responses and in milk fermentation, sialic acid and galactose are enzymatically removed, and the Gc1s isoform of DBP with the remaining GalNAc covalently bound to threonine 420 is known to stimulate macrophages [8].…”

Section: Introductionmentioning

confidence: 99%

Effect of glycosylated vitamin D binding protein complexed with oleic acid on human myeloma and Hodgkin’s lymphoma cultures

Branca¹,

Smith²,

Ward³

et al. 2015

Integr Cancer Sci Therap

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N-Acetylgalactosamine-glycosylated vitamin D binding protein (GalNAc-DBP) is known to stimulate macrophages and to directly inhibit angiogenesis and cancer cell growth in vitro. In this study, we evaluated the direct effect of GalNAc-DBP complexed with oleic acid on human multiple myeloma and Hodgkin's lymphoma cell lines (KMS-12-BM and L540 respectively) as well as the effect, on the same cell lines, of human spleen macrophages (CRL9853) previously activated by GalNAc-DBP complexed with oleic acid.Cell viability and living cell number were evaluated respectively by Tetrazolium dye cell viability assay and by Trypan Blue staining. Interactions between activated macrophages and cancer cells were studied by time lapse photography. Our results show that GalNAc-DBP complexed with oleic acid inhibits the proliferation of myeloma and Hodgkin's lymphoma cells in a dose-dependent manner. Furthermore, GalNAc-DBP complexed with oleic acid activates human spleen macrophages which in turn phagocytise cancer cells. In addition, we observed that GalNAc-DBP complexed with oleic acid activates human spleen macrophages in vivo as documented by color-doppler ultrasonography of the spleen. These results demonstrate that GalNAc-DBP complexed with oleic acid has a double effect on myeloma and Hodgkin's lymphoma cancer cells: a direct inhibition of their proliferation and viability and, at the same time, an efficient macrophage activation leading to a significant depletion of cancer cell population. Taken together, these results suggest that GalNAc-DBP complexed with oleic acid may prove effective in the integrative immunotherapy of multiple myeloma and Hodgkin's lymphoma.

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The glycosylation and characterization of the candidate Gc macrophage activating factor

Cited by 29 publications

References 60 publications

Behind the scenes of vitamin D binding protein: More than vitamin D binding

Behind the scenes of vitamin D binding protein: More than vitamin D binding

Variations in the Vitamin D-Binding Protein (DBP) Gene Are Related to Lower 25-Hydroxyvitamin D Levels in Healthy Girls: A Cross-Sectional Study

Effect of glycosylated vitamin D binding protein complexed with oleic acid on human myeloma and Hodgkin’s lymphoma cultures

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