| RRC ID |
43443
|
| 著者 |
Sogabe N, Oda K, Nakamura H, Orimo H, Watanabe H, Hosoi T, Goseki-Sone M.
|
| タイトル |
Molecular effects of the tissue-nonspecific alkaline phosphatase gene polymorphism (787T > C) associated with bone mineral density.
|
| ジャーナル |
Biomed Res
|
| Abstract |
Based on studies of hypophosphatasia, which is a systemic skeletal disorder resulting from tissuenonspecific alkaline phosphatase (TNSALP) deficiency, TNSALP was suggested to be indispensable for bone mineralization. Recently, we demonstrated that there was a significant difference in bone mineral density (BMD) among haplotypes, which was lowest among TNSALP (787T [Tyr-246Tyr]) homozygotes, highest among TNSALP (787T > C [Tyr246His]) homozygotes, and intermediate among heterozygotes. To analyze protein translated from the TNSALP gene 787T > C, we performed the biosynthesis of TNSALPs using TNSALP cDNA expression vectors. TNSALP (787T) and TNSALP (787T > C) were synthesized similarly as a high-mannose-type 66-kDa form, becoming an 80-kDa form. Expression of the human 787T > C TNSALP gene using the cultured mouse marrow stromal cell line ST2 demonstrated that the protein translated from 787T > C exhibited an ALP-specific activity similarly to that of 787T. Interestingly, the Km value for TNSALP in ST2 cells transfected with the 787T > C TNSALP gene was decreased significantly compared to that of cells carrying the 787T gene (P < 0.01). These results suggest that the significant difference in Km values between the proteins translated from 787T > C and 787T may contribute to regulatory effects on bone metabolism.
|
| 巻・号 |
29(4)
|
| ページ |
213-9
|
| 公開日 |
2008-8-1
|
| DOI |
10.2220/biomedres.29.213
|
| PII |
JST.JSTAGE/biomedres/29.213
|
| PMID |
18724009
|
| MeSH |
Alkaline Phosphatase / genetics*
Alkaline Phosphatase / metabolism
Animals
Bone Density / genetics*
Cell Line
Haplotypes
Humans
Hypophosphatasia / genetics
Hypophosphatasia / metabolism
Isoenzymes / genetics*
Isoenzymes / metabolism
Mice
Models, Molecular
Polymorphism, Genetic*
Protein Conformation
Stromal Cells / cytology
Stromal Cells / physiology
|
| IF |
1.429
|
| 引用数 |
17
|
|
WOS 分野
|
MEDICINE, RESEARCH & EXPERIMENTAL
|
| リソース情報 |
| ヒト・動物細胞 |
|
