論文 - 詳細
| RRC ID | 43963 |
|---|---|
| 著者 | Shizu R, Shindo S, Yoshida T, Numazawa S. |
| タイトル | MicroRNA-122 down-regulation is involved in phenobarbital-mediated activation of the constitutive androstane receptor. |
| ジャーナル | PLoS One |
| Abstract |
Constitutive androstane receptor (CAR) is a nuclear receptor that regulates the transcription of target genes, including CYP2B and 3A. Phenobarbital activates CAR, at least in part, in an AMP-activated protein kinase (AMPK)-dependent manner. However, the precise mechanisms underlying phenobarbital activation of AMPK are still unclear. In the present study, it was demonstrated that phenobarbital administration to mice decreases hepatic miR-122, a liver-enriched microRNA involved in both hepatic differentiation and function. The time-course change in the phenobarbital-mediated down-regulation of miR-122 was inversely correlated with AMPK activation. Phenobarbital decreased primary miR-122 to approximately 25% of the basal level as early as 1 h and suppressed transactivity of mir-122 promoter in HuH-7 cells, suggesting that the down-regulation occurred at the transcriptional level. AMPK activation by metformin or 5-aminoimidazole-4-carboxamide 1-β-D-ribonucleoside had no evident effect on miR-122 levels. An inhibitory RNA specific for miR-122 increased activated AMPK and CAR-mediated trancactivation of the phenobarbital-responsive enhancer module in HepG2 cells. Conversely, the reporter activity induced by the ectopic CAR was almost completely suppressed by co-transfection with the miR-122 mimic RNA. GFP-tagged CAR was expressed in the cytoplasm in addition to the nucleus in the majority of HuH-7 cells in which miR-122 was highly expressed. Co-transfection of the mimic or the inhibitor RNA for miR-122 further increased or decreased, respectively, the number of cells that expressed GFP-CAR in the cytoplasm. Taken together, these results suggest that phenobarbital-mediated down-regulation of miR-122 is an early and important event in the AMPK-dependent CAR activation and transactivation of its target genes. |
| 巻・号 | 7(7) |
| ページ | e41291 |
| 公開日 | 2012-1-1 |
| DOI | 10.1371/journal.pone.0041291 |
| PII | PONE-D-12-08761 |
| PMID | 22815988 |
| PMC | PMC3399820 |
| MeSH | Adenylate Kinase / metabolism Animals Constitutive Androstane Receptor Down-Regulation* Hep G2 Cells Humans Liver / metabolism Male Mice Mice, Inbred C3H MicroRNAs / biosynthesis* Phenobarbital / pharmacology* Plasmids / metabolism Receptors, Cytoplasmic and Nuclear / metabolism* Transcription Factors / metabolism Transcription, Genetic Transcriptional Activation |
| IF | 2.74 |
| 引用数 | 23 |
| WOS 分野 | 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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| 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 HuH-7 |