The Multifunctional Properties and Characteristics of Vitamin D-binding Protein

White, Peter; Cooke, Nancy E.

doi:10.1016/s1043-2760(00)00317-9

Cited by 335 publications

(297 citation statements)

References 67 publications

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“…Carrier proteins are unique for individual classes of steroid hormones. They include the vitamin D binding protein (DBP; the carrier for vitamin D metabolites) (White and Cooke, 2000), the sex hormone-binding globulin (SHBG; the carrier for androgens and estrogens) (Hammond and Bocchinfuso, 1995), and the corticosteroid-binding globulin (CBG; the carrier for glucocorticoids) (Scrocchi et al, 1993). Curiously, steroid hormones bound by carrier proteins are considered biologically inactive.…”

Section: Receptors For Steroid Carriers -Surface Binding Sites For Stmentioning

confidence: 99%

Cellular uptake of steroid carrier proteins—Mechanisms and implications

Willnow

Nykjaer

2010

Molecular and Cellular Endocrinology

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Steroid hormones are believed to enter cells solely by free diffusion through the plasma membrane. However, recent studies suggest the existence of cellular uptake pathways for carrier-bound steroids. Similar to the clearance of cholesterol via lipoproteins, these pathways involve the recognition of carrier proteins by endocytic receptors on the surface of target cells, followed by internalization and cellular delivery of the bound sterols. Here, we discuss the emerging concept that steroid hormones can selectively enter steroidogenic tissues by receptor-mediated endocytosis; and we discuss the implications of these uptake pathways for steroid hormone metabolism and action in vivo.

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Section: Receptors For Steroid Carriers -Surface Binding Sites For Stmentioning

confidence: 99%

Cellular uptake of steroid carrier proteins—Mechanisms and implications

Willnow

Nykjaer

2010

Molecular and Cellular Endocrinology

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“…These authors showed a strong correlation of higher, intermediate and lower circulating levels of 25(OH) 2 D 3 and 1,25(OH) 2 D 3 with Gc1-1, Gc1-2 and Gc2-2 phenotypes, respectively, in Danish Caucasian postmenopausal women population. In addition to storing and transporting vitamin D 3 hormones, VDBP also affects their pharmacokinetics (24) and plays a role in the sustained effective conversion of cutaneously derived vitamin D 3 into 25(OH) 2 D 3 . In addition to transporting vitamin D 3 , VDBP has multifunctional properties, including an important role in macrophage activation that is distinct from its vitamin D-binding ability.…”

Section: Vitamin D-binding Proteinmentioning

confidence: 99%

Genetic polymorphisms in vitamin D receptor, vitamin D-binding protein, Toll-like receptor 2, nitric oxide synthase 2, and interferon-γ genes and its association with susceptibility to tuberculosis

Leandro

Rocha

Cardoso

et al. 2009

Braz J Med Biol Res

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“…The chemotactic activity of C5a and C5a des Arg can be enhanced significantly by the vitamin D binding protein (DBP), a plasma protein also known as Gc-globulin (Binder et al, 1999;Kew and Webster, 1988;Metcalf et al, 1991;Perez et al, 1988;Zwahlen and Roth, 1990). DBP is a multifunctional and highly polymorphic plasma protein synthesized primarily in the liver, has a molecular mass of approximately 56 kDa and circulates in plasma at 6 to 7 μM (Gomme and Bertolini, 2004;White and Cooke, 2000). DBP is a member of the albumin (ALB), α-fetoprotein (AFP), and α-albumin/afamin (AFM) gene family and has the characteristic multiple disulfide-bonded, triple domain modular structure (White and Cooke, 2000).…”

Section: Introductionmentioning

confidence: 99%

“…DBP is a multifunctional and highly polymorphic plasma protein synthesized primarily in the liver, has a molecular mass of approximately 56 kDa and circulates in plasma at 6 to 7 μM (Gomme and Bertolini, 2004;White and Cooke, 2000). DBP is a member of the albumin (ALB), α-fetoprotein (AFP), and α-albumin/afamin (AFM) gene family and has the characteristic multiple disulfide-bonded, triple domain modular structure (White and Cooke, 2000). Besides functioning as a circulating vitamin D transport protein, it has been demonstrated that plasma DBP effectively scavenges G-actin released at sites of necrotic cell death and prevents polymerization of actin in the circulation (Gomme and Bertolini, 2004;White and Cooke, 2000).…”

Section: Introductionmentioning

confidence: 99%

“…DBP is a member of the albumin (ALB), α-fetoprotein (AFP), and α-albumin/afamin (AFM) gene family and has the characteristic multiple disulfide-bonded, triple domain modular structure (White and Cooke, 2000). Besides functioning as a circulating vitamin D transport protein, it has been demonstrated that plasma DBP effectively scavenges G-actin released at sites of necrotic cell death and prevents polymerization of actin in the circulation (Gomme and Bertolini, 2004;White and Cooke, 2000). Distinct binding regions within the 458 amino acid sequence of DBP have been identified.…”

Section: Introductionmentioning

confidence: 99%

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Selective inhibition of the C5a chemotactic cofactor function of the Vitamin D binding protein by 1,25(OH)2 Vitamin D3

Shah

DiMartino

Trujillo

et al. 2006

Molecular Immunology

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The vitamin D binding protein (DBP) is a multifunctional plasma protein that can significantly enhance the chemotactic response to complement fragment C5a. The chemotactic cofactor function of DBP requires cell surface binding in order to mediate this process. The goal of this study was to investigate the effect of ligating DBP with its two primary physiological ligands, vitamin D and Gactin, on both binding to neutrophils and the ability to enhance chemotaxis to C5a. There was no difference in neutrophil binding between of the holo (bound) forms versus the apo (unbound) form of radioiodinated DBP, indicating that the cell binding region of DBP likely is distinct from the vitamin D sterol and G-actin binding sites. Likewise, G-actin, 25(OH)D 3 , and G-actin plus 25(OH) D 3 bound to DBP did not alter its capacity to enhance chemotaxis toward C5a. However, the active form of vitamin D (1,25(OH) 2 D 3 ) completely eliminated the chemotactic cofactor function of DBP. Dose response curves demonstrated that as little as 1 pM 1,25(OH) 2 D 3 significantly inhibited chemotaxis enhancement. Moreover, at physiological concentrations 1,25(OH) 2 D 3 needs to be bound to DBP to mediate the inhibitory effect. Neutrophil chemotaxis to optimal concentrations of C5a, formyl peptide, CXCL8 or leukotriene B 4 was not altered by 1,25(OH) 2 D 3 indicating that the active vitamin does not have a global inhibitory effect on neutrophil chemotaxis. Finally, inhibition of cell surface alkaline phosphatase with sodium orthovanadate completely reversed the inhibitory effect of 1,25(OH) 2 D 3 . These results indicate that the cell binding and co-chemotactic functions of DBP are not altered when the protein binds G-actin and/or vitamin D. Furthermore, the co-chemotactic signal from DBP can be eliminated or counteracted by 1,25(OH) 2 D 3 .

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The Multifunctional Properties and Characteristics of Vitamin D-binding Protein

Cited by 335 publications

References 67 publications

Cellular uptake of steroid carrier proteins—Mechanisms and implications

Cellular uptake of steroid carrier proteins—Mechanisms and implications

Genetic polymorphisms in vitamin D receptor, vitamin D-binding protein, Toll-like receptor 2, nitric oxide synthase 2, and interferon-γ genes and its association with susceptibility to tuberculosis

Selective inhibition of the C5a chemotactic cofactor function of the Vitamin D binding protein by 1,25(OH)2 Vitamin D3

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