論文 - 詳細
| RRC ID | 54097 |
|---|---|
| 著者 | Oguro A, Inoue T, Kudoh SN, Imaoka S. |
| タイトル | 14,15-epoxyeicosatrienoic acid produced by cytochrome P450s enhances neurite outgrowth of PC12 and rat hippocampal neuronal cells. |
| ジャーナル | Pharmacol Res Perspect |
| Abstract |
Polyunsaturated fatty acids, such as arachidonic acid, are accumulated in brain and induce neuronal differentiation. Arachidonic acid is metabolized to epoxyeicosatrienoic acids (EETs) and hydroxyeicosatetraenoic acids (HETEs) by cytochrome P450s. In this study, we found that 14,15-EET and 20-HETE-enhanced NGF-induced rat pheochromocytoma PC12 cell neurite outgrowth even at the concentration of 100 nmol L-1. LC-MS analysis revealed that 14,15-EET was effectively produced from arachidonic acid by rat CYP2C11, 2C13, and 2C23, and these P450s were expressed in PC12 cells. An inhibitor of these P450s, ketoconazole, inhibited neurite outgrowth, whereas inhibition of soluble epoxide hydrolase, which hydrolyzes EETs to their corresponding diols enhanced neurite outgrowth. To determine the mechanism of neurite formation enhancement by arachidonic acid metabolites, we focused on transient receptor potential (TRP) channels expressed in PC12 cells. The TRPV4 inhibitor HC067047, but not the TRPV1 inhibitor capsazepine, inhibited the effects of 14,15-EET on neurite outgrowth of PC12. Furthermore, 14,15-EET increased the cytosolic calcium ion concentration and this increase was inhibited by HC067047. 14,15-EET also enhanced neurite outgrowth of primary cultured neuron from rat hippocampus. This study suggests that arachidonic acid metabolites produced by P450 contribute to neurite outgrowth through calcium influx. |
| 巻・号 | 6(5) |
| ページ | e00428 |
| 公開日 | 2018-10-1 |
| DOI | 10.1002/prp2.428 |
| PII | PRP2428 |
| PMID | 30237892 |
| PMC | PMC6141511 |
| MeSH | 8,11,14-Eicosatrienoic Acid / analogs & derivatives* 8,11,14-Eicosatrienoic Acid / metabolism 8,11,14-Eicosatrienoic Acid / pharmacology Animals Arachidonic Acid / metabolism Calcium / metabolism Capsaicin / analogs & derivatives Capsaicin / pharmacology Cytochrome P-450 Enzyme Inhibitors / pharmacology Cytochrome P-450 Enzyme System / metabolism* Embryo, Mammalian Hippocampus / cytology Hippocampus / drug effects* Hippocampus / metabolism Neurites / drug effects* Neuronal Outgrowth / drug effects* PC12 Cells Primary Cell Culture Rats Rats, Wistar TRPV Cation Channels / antagonists & inhibitors TRPV Cation Channels / metabolism |
| IF | 2.052 |
| 引用数 | 5 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 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 | PC-12(RCB0009) |