Linked Life Data

11580082

Source:http://linkedlifedata.com/resource/pubmed/id/11580082

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2001-10-2
pubmed:abstractText
It has been reported that vitamin K2 (menaquinone-4) promoted 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)-induced mineralization and enhanced gamma-carboxyglutamic acid (Gla)-containing osteocalcin accumulation in cultured human osteoblasts. In the present study, we investigated whether menaquinone-4 (MK-4) was metabolized in human osteoblasts to act as a cofactor of gamma-glutamyl carboxylase. Both conversions of MK-4 to MK-4 2,3-epoxide (epoxide) and epoxide to MK-4 were observed in cell extracts of cultured human osteoblasts. The effect of 1,25(OH)2D3 and warfarin on the vitamin K cycle to cultured osteoblasts were examined. With the addition of 1 nM 1,25(OH)2D3 or 25 microM warfarin in cultured osteoblasts, the yield of epoxide from MK-4 increased. However, the conversion of epoxide to MK-4 was strongly inhibited by the addition of warfarin (2.5-25 microM), whereas it was almost not inhibited by 1,25(OH)2D3 (0.1-10 nM). To clarify the mechanism for this phenomenon, a cell-free assay system was studied. Osteoblast microsomes were incubated with 10 microM epoxide in the presence or absence of warfarin and 1,25(OH)2D3. Epoxide reductase, one of the enzymes in the vitamin K cycle was strongly inhibited by warfarin (2.5-25 microM), whereas it was not affected by 1,25(OH)2D3 (0.1-1 nM). Moreover, there was no effect of pretreatment of osteoblasts with 1 nM 1,25(OH)2D3 on the activity of epoxide reductase. However, the activity of epoxidase, that is the gamma-glutamyl carboxylase was induced by the pretreatment of osteoblasts with 1 nM 1,25(OH)2D3. In the present study, it was demonstrated that the vitamin K metabolic cycle functions in human osteoblasts as well as in the liver, the post-translational mechanism, by which 1,25(OH)2D3 caused mineralization in cooperation with vitamin K2 was clarified.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0937-941X
pubmed:author
pubmed:issnType
Print
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
680-7
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
1,25-Dihydroxyvitamin D3 promotes vitamin K2 metabolism in human osteoblasts.
pubmed:affiliation
Department of Nutrition, Tokyo Metropolitan Institute of Gerontology, Japan.
pubmed:publicationType
Journal Article