論文 - 詳細
| RRC ID | 51810 |
|---|---|
| 著者 | Uesugi S, Muroi M, Kondoh Y, Shiono Y, Osada H, Kimura KI. |
| タイトル | Allantopyrone A activates Keap1-Nrf2 pathway and protects PC12 cells from oxidative stress-induced cell death. |
| ジャーナル | J Antibiot (Tokyo) |
| Abstract |
Keap1-Nrf2 system is known as a sensor of electrophilic compounds, and protects cells from oxidative stress through induction of various antioxidant enzymes. We found by proteomic analysis that allantopyrone A, a metabolite isolated from an endophytic fungus, upregulates the expression of proteins that are regulated by the transcription factor Nrf2. Indeed, allantopyrone A increased the antioxidant enzyme heme oxygenase-1 in PC12 cells. Moreover, it induced localization of Nrf2 in the nucleus. Affinity purification of allantopyrone A-binding protein showed that this compound could bind directly to Keap1. Allantopyrone A suppressed intracellular reactive oxygen species level and cell death induced by H2O2 in PC12 cells. These results indicate that allantopyrone A protects PC12 cells from oxidative stress-induced cell death through direct binding with Keap1 and activation of the Keap1-Nrf2 pathway. |
| 巻・号 | 70(4) |
| ページ | 429-434 |
| 公開日 | 2017-4-1 |
| DOI | 10.1038/ja.2016.99 |
| PII | ja201699 |
| PMID | 27507633 |
| MeSH | Animals Antioxidants / pharmacology Cell Death / drug effects* Heme Oxygenase-1 / metabolism Humans Hydrogen Peroxide / pharmacology Kelch-Like ECH-Associated Protein 1 / drug effects Kelch-Like ECH-Associated Protein 1 / metabolism* NF-E2-Related Factor 2 / drug effects NF-E2-Related Factor 2 / metabolism* Oxidants / pharmacology Oxidative Stress / drug effects* PC12 Cells Proteomics Pyrones / pharmacology* Rats Reactive Oxygen Species / metabolism Signal Transduction / drug effects* Sulfhydryl Compounds / pharmacology Up-Regulation / drug effects |
| IF | 2.446 |
| 引用数 | 8 |
| リソース情報 | |
| ヒト・動物細胞 | PC-12(RCB0009) |