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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
|
| pubmed:dateCreated |
1994-1-24
|
| pubmed:abstractText |
The vitamin K-dependent clotting factors II, VII, IX, and X are proteins which undergo gamma-carboxylation of specific glutamic acid residues prior to secretion from the liver. These unique Ca2+ binding amino acids allow the interaction of the proteins with cell surface phospholipids, a function that is crucial for expression of full procoagulant activity of the proteins. The N-terminal region of the molecule contains the gamma-carboxylation sites and is termed the Gla-domain. A preliminary observation in rats suggested that mineralized bone accumulated activated recombinant FVII (rFVIIa: NovoSeven) as well as the non-activated, single chain rFVII. The present study investigated the role of the Gla-domain in the accumulation of rFVII in bone, as well as the influence of the activation state of FVII on this phenomenon. Rats were treated with 125I-labelled rFVII, rFVIIa, Gla-domainless rFVIIa, factor IX, iodide, or recombinant human growth hormone (rhGH). Following sacrifice, radioactivity was measured in mineralized bone, among other tissues. Following administration of 125I-radiolabelled rFVII, rFVIIa and factor IX, but not Gla-domainless rFVIIa, iodide or rhGH, extensive sequestration occurred in endochondrally as well as intramenbranously ossified bones. The results indicate that the proteins containing a Gla-domain, and only these, are sequestered in bone. Additionally, the normally occurring form of FVII in the circulation, the single-chain FVII, exhibited similar kinetics in rat bone and plasma, as the two-chain rFVIIa. The half-life of rFVII/rFVIIa in mineralized bone was between 3 and 4 days, implying that significant bone accumulation of the factor will take place at steady state.(ABSTRACT TRUNCATED AT 250 WORDS)
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Factor IX,
http://linkedlifedata.com/resource/pubmed/chemical/Factor VIIa,
http://linkedlifedata.com/resource/pubmed/chemical/Glutamates,
http://linkedlifedata.com/resource/pubmed/chemical/Glutamic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Growth Hormone,
http://linkedlifedata.com/resource/pubmed/chemical/Iodine Radioisotopes,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Vitamin K
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Sep
|
| pubmed:issn |
0901-9928
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
73
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
127-32
|
| pubmed:dateRevised |
2005-11-17
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| pubmed:meshHeading |
pubmed-meshheading:7903449-Animals,
pubmed-meshheading:7903449-Bone and Bones,
pubmed-meshheading:7903449-Calcification, Physiologic,
pubmed-meshheading:7903449-Cricetinae,
pubmed-meshheading:7903449-Factor IX,
pubmed-meshheading:7903449-Factor VIIa,
pubmed-meshheading:7903449-Female,
pubmed-meshheading:7903449-Glutamates,
pubmed-meshheading:7903449-Glutamic Acid,
pubmed-meshheading:7903449-Growth Hormone,
pubmed-meshheading:7903449-Iodine Radioisotopes,
pubmed-meshheading:7903449-Kinetics,
pubmed-meshheading:7903449-Male,
pubmed-meshheading:7903449-Rats,
pubmed-meshheading:7903449-Rats, Wistar,
pubmed-meshheading:7903449-Recombinant Proteins,
pubmed-meshheading:7903449-Structure-Activity Relationship,
pubmed-meshheading:7903449-Vitamin K
|
| pubmed:year |
1993
|
| pubmed:articleTitle |
Accumulation of the recombinant factor VIIa in rat bone: importance of the Gla-domain and relevance to factor IX, another vitamin K-dependent clotting factor.
|
| pubmed:affiliation |
Biopharmaceuticals Division, Novo Nordisk A/S, Gentofte, Denmark.
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| pubmed:publicationType |
Journal Article
|