論文 - 詳細
| RRC ID | 18523 |
|---|---|
| 著者 | Hamada N, Tanaka A, Fujita Y, Itoh T, Ono Y, Kitagawa Y, Tomimori N, Kiso Y, Akao Y, Nozawa Y, Ito M. |
| タイトル | Involvement of heme oxygenase-1 induction via Nrf2/ARE activation in protection against H2O2-induced PC12 cell death by a metabolite of sesamin contained in sesame seeds. |
| ジャーナル | Bioorg Med Chem |
| Abstract |
Induction of phase II antioxidant enzymes by activation of Nrf2/ARE (antioxidant response element) signaling has been considered as a promising strategy to combat with oxidative stress-related diseases. In the present study, we tested for potential effects of sesamin, a major lignan contained in sesame seeds, its stereoisomer episesamin, and their metabolites on Nrf2/ARE activation in rat pheochromocytoma PC12 cells. Luciferase reporter assays showed that primary metabolites of sesamin and episesamin, SC-1 and EC-1 were the most potent ARE activators among all tested compounds. SC-1 {(1R,2S,5R,6S)-6-(3,4-dihydroxyphenyl)-2-(3,4-methylenedioxyphenyl)-3,7-dioxabicyclo-[3,3,0]octane} enhanced nuclear translocation of Nrf2 and up-regulated expression of phase II antioxidant enzymes including heme oxygenase-1 (HO-1). Treatment with SC-1 resulted in increased phosphorylation of p38 MAP kinase and transient increase in intracellular ROS levels. N-acetylcysteine (NAC) treatment abolished p38 phosphorylation as well as HO-1 induction caused by SC-1, indicating that ROS are upstream signals of p38 in Nrf2/ARE activation by SC-1. Furthermore, preconditioning with SC-1 attenuated H(2)O(2)-induced cell death in a dose-dependent manner. Finally, treatment with a HO-1 inhibitor, Zn-protoporphyrin (ZnPP), and overexpression of a dominant-negative mutant of Nrf2 diminished SC-1-mediated neuroprotection. Our results demonstrate that SC-1 is capable of protecting against oxidative stress-induced neuronal cell death in part through induction of HO-1 via Nrf2/ARE activation, suggesting its potential to reduce oxidative stress and ameliorate oxidative stress-related neurodegenerative diseases. |
| 巻・号 | 19(6) |
| ページ | 1959-65 |
| 公開日 | 2011-3-15 |
| DOI | 10.1016/j.bmc.2011.01.059 |
| PII | S0968-0896(11)00088-5 |
| PMID | 21345685 |
| MeSH | Animals Apoptosis* Dioxoles / chemistry Dioxoles / metabolism* Dioxoles / pharmacology Heme Oxygenase-1 / chemistry Heme Oxygenase-1 / metabolism* Hydrogen Peroxide / metabolism* Lignans / chemistry Lignans / metabolism* Lignans / pharmacology NF-E2-Related Factor 2 / metabolism* PC12 Cells Rats Seedlings / chemistry Sesamum / chemistry* |
| IF | 3.073 |
| 引用数 | 29 |
| WOS 分野 | CHEMISTRY, MEDICINAL CHEMISTRY, ORGANIC 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 | 1 |
| 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) |