論文 - 詳細
| RRC ID | 38333 |
|---|---|
| 著者 | Abiko Y, Shinkai Y, Sumi D, Kumagai Y. |
| タイトル | Reduction of arsenic-induced cytotoxicity through Nrf2/HO-1 signaling in HepG2 cells. |
| ジャーナル | J Toxicol Sci |
| Abstract |
Our previous study indicated that Nrf2 is a key transcription factor in cellular defenses against inorganic arsenite (iAsIII). However, the role of heme oxygenase-1 (HO-1), which is regulated by Nrf2, in iAsIII-induced cytotoxicity is poorly understood. To address this issue, we examined the contribution of HO-1 to iAsIII-mediated Nrf2 activation and in protection against iAsIII cytotoxicity in HepG2 cells. Exposure of HepG2 cells to iAsIII (10 microM) caused persistent induction of HO-1 accompanied by prolonged Nrf2 activation, whereas siRNA-mediated knockdown of HO-1 decreased prolonged Nrf2 activation. Pretreatment with either HO-1 siRNA or HO inhibitor (tin protoporphyrin IX) significantly enhanced iAsIII-induced cytotoxicity. These results suggest that iAsIII-induced HO-1 appears, at least in part, to act as a positive feedback regulator of Nrf2 activation, thereby diminishing its cytotoxicity in HepG2 cells. |
| 巻・号 | 35(3) |
| ページ | 419-23 |
| 公開日 | 2010-6-1 |
| DOI | 10.2131/jts.35.419 |
| PII | JST.JSTAGE/jts/35.419 |
| PMID | 20519851 |
| MeSH | Arsenites / toxicity* Enzyme Induction / drug effects Heme Oxygenase-1 / antagonists & inhibitors Heme Oxygenase-1 / genetics Heme Oxygenase-1 / metabolism Heme Oxygenase-1 / physiology* Hep G2 Cells Humans NF-E2-Related Factor 2 / metabolism NF-E2-Related Factor 2 / physiology* Protoporphyrins / pharmacology RNA, Small Interfering / pharmacology Signal Transduction / physiology* |
| IF | 1.737 |
| 引用数 | 24 |
| WOS 分野 | TOXICOLOGY |
| 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 | Hep G2(RCB1648) |