論文 - 詳細
| RRC ID | 80080 |
|---|---|
| 著者 | Adachi T, Nakagawa H, Chung I, Hagiya Y, Hoshijima K, Noguchi N, Kuo MT, Ishikawa T. |
| タイトル | Nrf2-dependent and -independent induction of ABC transporters ABCC1, ABCC2, and ABCG2 in HepG2 cells under oxidative stress. |
| ジャーナル | J Exp Ther Oncol |
| Abstract |
Nrf2, an NF-E2-related transcription factor, plays a critical role in transcriptional upregulation of many target genes, including those for metabolizing enzymes and transporters essential for cellular defense in response to oxidative and/or electrophilic stress. In the present study, we have studied the potential involvement of Nrf2 in induction of human ABC transporter genes under oxidative stress. We created a real-time PCR primer set to quantitatively investigate the induction of human ABC transporters by a redox-active compound tert-butylhydroquinone (tBHQ) in HepG2 cells. We found that mRNA levels of ABCC1, ABCC2, ABCC3, and ABCG2 were significantly elevated in dose- and time-dependent manners. Translocation of Nrf2 into the nuclei occurred concomitantly with the induction of ABCC1 and ABCC2 as well as both heavy and light chains of gamma-glutamylcysteine synthetase (gamma-GCSh and gamma-GCSI) during tBHQ treatments. To examine the potential involvement of Nrf2 in upregulation of the ABC transporters, we treated cells with siRNA to knockdown the expression of Nrf2. Under such Nrf2-knockdown conditions, tBHQ-induced mRNA levels of ABCC2 and ABCG2 were significantly suppressed as were mRNA levels of gamma-GCSh and gamma-GCSI. Interestingly, however, the elevated mRNA level of ABCC1 was little affected by Nrf2 siRNA treatment. We also addressed the involvement of Keap1, which is a negative regulator of Nrf2 by retrieving it in the cytoplasm. When HepG2 cells were treated with Keap1-specifc siRNA, a significant increase was observed in mRNA levels of ABCC1, ABCC2, and ABCG2 as well as gamma-GCSI, suggesting that induction of ABCC2 and ABCG2 by tBHQ is mediated by the Nrf2/Keap1 system, whereas the induction of ABCC1 may involve a Keap1-dependent but Nrf2-independent mechanism. |
| 巻・号 | 6(4) |
| ページ | 335-48 |
| 公開日 | 2007-1-1 |
| PMID | 18038766 |
| MeSH | Cell Line, Tumor Humans Hydroquinones / pharmacology Intracellular Signaling Peptides and Proteins / physiology Kelch-Like ECH-Associated Protein 1 Liver Neoplasms / metabolism Liver Neoplasms / pathology Membrane Transport Proteins / genetics* Multidrug Resistance-Associated Protein 2 Multidrug Resistance-Associated Proteins / genetics* NF-E2-Related Factor 2 / physiology* Oxidative Stress* RNA, Messenger / analysis* |
| 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 | 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 | Hep G2(RCB1648) |