論文 - 詳細
| RRC ID | 19159 |
|---|---|
| 著者 | Hashimoto K, Ishima T. |
| タイトル | A novel target of action of minocycline in NGF-induced neurite outgrowth in PC12 cells: translation initiation [corrected] factor eIF4AI. |
| ジャーナル | PLoS One |
| Abstract |
BACKGROUND:Minocycline, a second-generation tetracycline antibiotic, has potential activity for the treatment of several neurodegenerative and psychiatric disorders. However, its mechanisms of action remain to be determined. METHODOLOGY/PRINCIPAL FINDINGS:We found that minocycline, but not tetracycline, significantly potentiated nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells, in a concentration dependent manner. Furthermore, we found that the endoplasmic reticulum protein inositol 1,4,5-triphosphate (IP3) receptors and several common signaling molecules (PLC-γ, PI3K, Akt, p38 MAPK, c-Jun N-terminal kinase (JNK), mammalian target of rapamycin (mTOR), and Ras/Raf/ERK/MAPK pathways) might be involved in the active mechanism of minocycline. Moreover, we found that a marked increase of the eukaryotic translation initiation factor eIF4AI protein by minocycline, but not tetracycline, might be involved in the active mechanism for NGF-induced neurite outgrowth. CONCLUSIONS/SIGNIFICANCE:These findings suggest that eIF4AI might play a role in the novel mechanism of minocycline. Therefore, agents that can increase eIF4AI protein would be novel therapeutic drugs for certain neurodegenerative and psychiatric diseases. |
| 巻・号 | 5(11) |
| ページ | e15430 |
| 公開日 | 2010-11-8 |
| DOI | 10.1371/journal.pone.0015430 |
| PMID | 21151481 |
| PMC | PMC2975708 |
| MeSH | Animals Anti-Bacterial Agents / pharmacology Blotting, Western Dose-Response Relationship, Drug Doxycycline / pharmacology Drug Synergism Eukaryotic Initiation Factor-4A / genetics Eukaryotic Initiation Factor-4A / metabolism Immunohistochemistry Inositol 1,4,5-Trisphosphate Receptors / antagonists & inhibitors Inositol 1,4,5-Trisphosphate Receptors / metabolism Macrocyclic Compounds / pharmacology Microtubule-Associated Proteins / metabolism Minocycline / pharmacology* Mitogen-Activated Protein Kinases / metabolism Nerve Growth Factor / pharmacology* Neurites / drug effects* Neurites / physiology Oxazoles / pharmacology PC12 Cells RNA Interference Rats Signal Transduction / drug effects Tetracyclines / pharmacology raf Kinases / metabolism ras Proteins / metabolism |
| IF | 2.74 |
| 引用数 | 37 |
| WOS 分野 | NEUROSCIENCES |
| リソース情報 | |
| ヒト・動物細胞 | PC-12(RCB0009) |