論文 - 詳細
| RRC ID | 43223 |
|---|---|
| 著者 | Ishizawa M, Matsunawa M, Adachi R, Uno S, Ikeda K, Masuno H, Shimizu M, Iwasaki K, Yamada S, Makishima M. |
| タイトル | Lithocholic acid derivatives act as selective vitamin D receptor modulators without inducing hypercalcemia. |
| ジャーナル | J Lipid Res |
| Abstract |
1alpha,25-Dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], a vitamin D receptor (VDR) ligand, regulates calcium homeostasis and also exhibits noncalcemic actions on immunity and cell differentiation. In addition to disorders of bone and calcium metabolism, VDR ligands are potential therapeutic agents in the treatment of immune disorders, microbial infections, and malignancies. Hypercalcemia, the major adverse effect of vitamin D(3) derivatives, limits their clinical application. The secondary bile acid lithocholic acid (LCA) is an additional physiological ligand for VDR, and its synthetic derivative, LCA acetate, is a potent VDR agonist. In this study, we found that an additional derivative, LCA propionate, is a more selective VDR activator than LCA acetate. LCA acetate and LCA propionate induced the expression of the calcium channel transient receptor potential vanilloid type 6 (TRPV6) as effectively as that of 1alpha,25-dihydroxyvitamin D(3) 24-hydroxylase (CYP24A1), whereas 1,25(OH)(2)D(3) was more effective on TRPV6 than on CYP24A1 in intestinal cells. In vivo experiments showed that LCA acetate and LCA propionate effectively induced tissue VDR activation without causing hypercalcemia. These bile acid derivatives have the ability to function as selective VDR modulators. |
| 巻・号 | 49(4) |
| ページ | 763-72 |
| 公開日 | 2008-4-1 |
| DOI | 10.1194/jlr.M700293-JLR200 |
| PII | S0022-2275(20)42389-2 |
| PMID | 18180267 |
| MeSH | Animals Bile Acids and Salts / metabolism Body Weight / drug effects Cell Line Gene Expression Regulation / drug effects Humans Hypercalcemia / chemically induced Hypercalcemia / metabolism Lithocholic Acid / analogs & derivatives* Lithocholic Acid / pharmacology* Male Mice Mice, Inbred C57BL Molecular Structure Receptors, Calcitriol / antagonists & inhibitors* Receptors, Calcitriol / genetics Receptors, Calcitriol / metabolism* |
| IF | 4.483 |
| 引用数 | 74 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 9 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | CACO-2(RCB0988) MG-63(RCB1890) RCB1890(RCB0426) |