論文 - 詳細
| RRC ID | 11017 |
|---|---|
| 著者 | Masaike Y, Takagi T, Hirota M, Yamada J, Ishihara S, Yung TM, Inoue T, Sawa C, Sagara H, Sakamoto S, Kabe Y, Takahashi Y, Yamaguchi Y, Handa H. |
| タイトル | Identification of dynamin-2-mediated endocytosis as a new target of osteoporosis drugs, bisphosphonates. |
| ジャーナル | Mol Pharmacol |
| Abstract |
Nitrogen-containing bisphosphonates are pyrophosphate analogs that have long been the preferred prescription for treating osteoporosis. Although these drugs are considered inhibitors of prenylation and are believed to exert their effects on bone resorption by disrupting the signaling pathways downstream of prenylated small GTPases, this explanation seems to be insufficient. Because other classes of prenylation inhibitors have recently emerged as potential antiviral therapeutic agents, we first investigated here the effects of bisphosphonates on simian virus 40 and adenovirus infections and, to our surprise, found that viral infections are suppressed by bisphosphonates through a prenylation-independent pathway. By in-house affinity-capture techniques, dynamin-2 was identified as a new molecular target of bisphosphonates. We present evidence that certain bisphosphonates block endocytosis of adenovirus and a model substrate by inhibiting GTPase activity of dynamin-2. Hence, this study has uncovered a previously unknown mechanism of action of bisphosphonates and offers potential novel use for these drugs. |
| 巻・号 | 77(2) |
| ページ | 262-9 |
| 公開日 | 2010-2-1 |
| DOI | 10.1124/mol.109.059006 |
| PII | mol.109.059006 |
| PMID | 19903825 |
| MeSH | Animals Bone Density Conservation Agents / administration & dosage* Bone Density Conservation Agents / pharmacology Cattle Cell Line Diphosphonates / administration & dosage* Diphosphonates / pharmacology Drug Delivery Systems* / trends Dynamin II / antagonists & inhibitors Dynamin II / physiology* Endocytosis / drug effects* Endocytosis / physiology* HeLa Cells Humans Mice Osteoporosis / drug therapy Osteoporosis / metabolism* Osteoporosis / pathology* Protein Prenylation / drug effects Protein Prenylation / physiology Signal Transduction / drug effects Signal Transduction / physiology |
| IF | 3.664 |
| 引用数 | 16 |
| WOS 分野 | PHARMACOLOGY & PHARMACY |
| 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 | X(Twitter) |
| 各媒体での言及数の合計 | 7 |
| 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 | |
| 遺伝子材料 | AxCA Luc+ (RDB02453) |