Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P02774 (Gc-globulin)
 196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vitamin D-binding protein (DBP) is a multi-functional serum protein that is converted to vitamin D-binding protein-macrophage activating factor (DBP-maf) by post-translational modification. DBP-maf is a new cytokine that mediates bone resorption by activating osteoclasts, which are responsible for resorption of bone. Defective osteoclast activation leads to disorders like osteopetrosis, characterized by excessive accumulation of bone mass. Previous studies demonstrated that two nonallelic mutations in the rat with osteopetrosis have independent defects in the cascade involved in the conversion of DBP to DBP-maf. The skeletal defects associated with osteopetrosis are corrected in these mutants with in vivo DBP-maf treatment. This study evaluates the effects of various forms of DBP-maf (native, recombinant, and 25-hydroxyvitamin D(3) bound) on osteoclast function in vitro in order to determine some of the structural requirements of this protein that relate to bone resorbing activities. Osteoclast activity was determined by evaluating pit formation using osteoclasts, isolated from the long bones of newborn rats, incubated on calcium phosphate coated, thin film, Ostologic MultiTest Slides. Incubation of osteoclasts with ex vivo generated native DBP-maf resulted in a dose dependent, statistically significant, activation of the osteoclasts. The activation was similar whether or not the vitamin D binding site of the DBP-maf was occupied. The level of activity in response to DBP-maf was greater than that elicited by optimal doses of other known stimulators (PTH and 1,25(OH(2)D(3)) of osteoclast function. Furthermore, another potent macrophage activating factor, interferon--gamma, had no effect on osteoclast activity. The activated form of a full length recombinant DBP, expressed in E. coli showed no activity in the in vitro assay. Contrary to this finding, baculovirus-expressed recombinant DBP-maf demonstrated significant osteoclast activating activity. The normal conversion of DBP to DBP-maf requires the selective removal of galactose and sialic acid from the third domain of the protein. Hence, the differential effects of the two recombinant forms of DBP-maf is most likely related to glycosylation; E. coli expressed recombinant DBP is non-glycosylated, whereas the baculovirus expressed form is glycosylated. These data support the essential role of glycosylation for the osteoclast activating property of DBP-maf.
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PMID:Baculovirus-expressed vitamin D-binding protein-macrophage activating factor (DBP-maf) activates osteoclasts and binding of 25-hydroxyvitamin D(3) does not influence this activity. 1125 36

Environmental cadmium (Cd) pollution and its effects on human health are still important issues. The most severe and representative manifestation of chronic Cd intoxication is Itai-itai disease, which is a syndrome that includes renal tubular dysfunction, osteomalacia, and generalized pain due to multiple bone fractures. The whole mechanism of how renal dysfunction relates to the development of bone lesions is unresolved. Vitamin D-binding protein (DBP) binds, transports and activates vitamin D, which plays a major role in calcium homeostasis and bone turnover. In this study, we measured urinary DBP levels and investigated their relationship to the markers of renal tubular dysfunction in the inhabitants of a Cd-polluted Jinzu River basin in Toyama Prefecture, Japan (Cd group). We also investigated age-matched subjects from an area known to have lower levels of Cd pollution (reference group). Urinary DBP was measured by a fluorometric enzyme-linked immunosorbent assay (ELISA), which was established in our laboratory. Significantly higher levels of urinary DBP were observed in the Cd group compared to the reference group. We observed significant positive correlations between urinary levels of DBP and renal tubular dysfunction markers in both groups. In the Cd group, urinary levels of DBP had a negative correlation with serum phosphate value. These results indicate that excretion of urinary DBP is increased after long-term Cd exposure and that the loss of DBP in urine may be linked to renal tubular dysfunction and possibly bone lesions in the inhabitants of Cd-polluted areas.
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PMID:Elevated urinary levels of vitamin D-binding protein in the inhabitants of a cadmium polluted area, Jinzu River basin, Japan. 1734 52