論文 - 詳細
| RRC ID | 30497 |
|---|---|
| 著者 | Bae SH, Sung SH, Oh SY, Lim JM, Lee SK, Park YN, Lee HE, Kang D, Rhee SG. |
| タイトル | Sestrins activate Nrf2 by promoting p62-dependent autophagic degradation of Keap1 and prevent oxidative liver damage. |
| ジャーナル | Cell Metab |
| Abstract |
Sestrins (Sesns) protect cells from oxidative stress. The mechanism underlying the antioxidant effect of Sesns has remained unknown, however. The Nrf2-Keap1 pathway provides cellular defense against oxidative stress by controlling the expression of antioxidant enzymes. We now show that Sesn1 and Sesn2 interact with the Nrf2 suppressor Keap1, the autophagy substrate p62, and the ubiquitin ligase Rbx1 and that the antioxidant function of Sesns is mediated through activation of Nrf2 in a manner reliant on p62-dependent autophagic degradation of Keap1. Sesn2 was upregulated in the liver of mice subjected to fasting or subsequent refeeding with a high-carbohydrate, fat-free diet, whereas only refeeding promoted Keap1 degradation and Nrf2 activation, because only refeeding induced p62 expression. Ablation of Sesn2 blocked Keap1 degradation and Nrf2 activation induced by refeeding and thereby increased the susceptibility of the liver to oxidative damage resulting from the acute stimulation of lipogenesis associated with refeeding. |
| 巻・号 | 17(1) |
| ページ | 73-84 |
| 公開日 | 2013-1-8 |
| DOI | 10.1016/j.cmet.2012.12.002 |
| PII | S1550-4131(12)00493-7 |
| PMID | 23274085 |
| MeSH | Adaptor Proteins, Signal Transducing / metabolism* Animals Autophagy Carrier Proteins / metabolism Cell Cycle Proteins / metabolism Cytoskeletal Proteins / metabolism* HCT116 Cells HEK293 Cells HeLa Cells Humans Kelch-Like ECH-Associated Protein 1 Liver / metabolism* Liver / physiopathology Male Mice Mice, Inbred C57BL NF-E2-Related Factor 2 / metabolism* Nuclear Proteins Oxidative Stress Peroxidases Protein Binding Proteins / metabolism* Transcription Factor TFIIH Transcription Factors / metabolism* Transfection Up-Regulation |
| IF | 21.567 |
| 引用数 | 223 |
| WOS 分野 | ENDOCRINOLOGY & METABOLISM CELL 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 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 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 | |
| 実験動物マウス | RBRC01390 |