論文 - 詳細
| RRC ID | 18928 |
|---|---|
| 著者 | Minase T, Ishima T, Itoh K, Hashimoto K. |
| タイトル | Potentiation of nerve growth factor-induced neurite outgrowth by the ROCK inhibitor Y-27632: a possible role of IP₃ receptors. |
| ジャーナル | Eur J Pharmacol |
| Abstract |
ROCK, a serine/threonine protein kinase that has been identified as a Rho GTP-binding protein, is a promising target for neuropsychiatric disorders. The selective ROCK inhibitor Y-27632 has been shown to induce neurite outgrowth in PC12 cells. However, the precise cellular and molecular mechanisms underlying ROCK inhibition-induced neurite outgrowth are not fully understood. In this study, we examined the roles of cellular signaling pathways in the potentiation of nerve growth factor (NGF)-induced neurite outgrowth by Y-27632. Y-27632 significantly potentiated NGF (2.5 ng/ml)-induced neurite outgrowth in PC12 cells, in a concentration-dependent manner. Furthermore, another ROCK inhibitor, H-1152, and the Rho inhibitor botulinum exoenzyme C3 also potentiated NGF (2.5 ng/ml)-induced neurite outgrowth. The effects by Y-27632 were antagonized by co-administration of inositol 1,4,5-trisphosphate (IP(3)) receptor antagonists (xestospongin C or 2-aminoethoxydiphenylborate (2-APB)). Moreover, the potentiation by Y-27632 was blocked by co-administration of the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 or an Akt inhibitor. In contrast, the specific inhibitors of phospholipase C (PLC-γ), p38MAPK, c-Jun N-terminal kinase (JNK), and the Ras/Raf/mitogen-activated protein kinase (MAPK) signaling pathways did not affect the potentiation of NGF-induced neurite outgrowth by Y-27632. The results of double-staining immunocytochemistry suggested that both ROCK1 and type-1 IP₃ receptors may be co-localized in the cell body of PC12 cells. In conclusion, these findings suggest that IP₃ receptors and PI3K-Akt signaling pathways might be involved in the mechanisms of potentiation of NGF-induced neurite outgrowth by ROCK inhibitors. |
| 巻・号 | 648(1-3) |
| ページ | 67-73 |
| 公開日 | 2010-12-1 |
| DOI | 10.1016/j.ejphar.2010.09.007 |
| PII | S0014-2999(10)00887-3 |
| PMID | 20854802 |
| MeSH | Amides / pharmacology* Animals Drug Synergism Inositol 1,4,5-Trisphosphate Receptors / metabolism* MAP Kinase Signaling System / drug effects Nerve Growth Factor / pharmacology* Neurites / drug effects* Neurites / enzymology Neurites / metabolism* PC12 Cells Piperazines / pharmacology Protein Kinase Inhibitors / pharmacology* Pyridines / pharmacology* Rats Receptor, trkA / metabolism rho GTP-Binding Proteins / antagonists & inhibitors rho-Associated Kinases / antagonists & inhibitors* |
| IF | 3.263 |
| 引用数 | 26 |
| 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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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | PC-12(RCB0009) |