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Post-transcriptional regulation of human pregnane X receptor by micro-RNA affects the expression of cytochrome P450 3A4.
https://doi.org/10.24517/00014795
https://doi.org/10.24517/000147959578a797-8423-4ebe-b512-645025ff505b
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
PH-PR-NAKAJIMA-M-9674.pdf (1.3 MB)
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||||
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| 公開日 | 2017-10-03 | |||||||
| タイトル | ||||||||
| タイトル | Post-transcriptional regulation of human pregnane X receptor by micro-RNA affects the expression of cytochrome P450 3A4. | |||||||
| 言語 | ||||||||
| 言語 | eng | |||||||
| 資源タイプ | ||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||||
| 資源タイプ | journal article | |||||||
| ID登録 | ||||||||
| ID登録 | 10.24517/00014795 | |||||||
| ID登録タイプ | JaLC | |||||||
| 著者 |
Takagi, Shingo
× Takagi, Shingo× Nakajima, Miki× Mohri, Takuya× Yokoi, Tsuyoshi |
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| 著者別表示 |
中嶋, 美紀
× 中嶋, 美紀
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| 提供者所属 | ||||||||
| 内容記述タイプ | Other | |||||||
| 内容記述 | 金沢大学ナノ生命科学研究所 / 金沢大学医薬保健研究域薬学系 | |||||||
| 書誌情報 |
The Journal of biological chemistry 巻 283, 号 15, p. 9674-9680, 発行日 2008-04-11 |
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| ISSN | ||||||||
| 収録物識別子タイプ | ISSN | |||||||
| 収録物識別子 | 0021-9258 | |||||||
| NCID | ||||||||
| 収録物識別子タイプ | NCID | |||||||
| 収録物識別子 | AA00251083 | |||||||
| DOI | ||||||||
| 関連タイプ | isVersionOf | |||||||
| 識別子タイプ | DOI | |||||||
| 関連識別子 | 10.1074/jbc.M709382200 | |||||||
| 出版者 | ||||||||
| 出版者 | American Society for Biochemistry and Molecular Biology | |||||||
| 抄録 | ||||||||
| 内容記述タイプ | Abstract | |||||||
| 内容記述 | Pregnane X receptor (PXR) is a major transcription factor regulating the inducible expression of a variety of transporters and drug-metabolizing enzymes, including CYP3A4 (cytochrome P450 3A4). We first found that the PXR mRNA level was not correlated with the PXR protein level in a panel of 25 human livers, indicating the involvement of post-transcriptional regulation. Notably, a potential miR-148a recognition element was identified in the 3'-untranslated region of human PXR mRNA. We investigated whether PXR might be regulated by miR-148a. A reporter assay revealed that miR-148a could recognize the miR-148a recognition element of PXR mRNA. The PXR protein level was decreased by the overexpression of miR-148a, whereas it was increased by inhibition of miR-148a. The miR-148a-dependent decrease of PXR protein attenuated the induction CYP3A4 mRNA. Furthermore, the translational efficiency of PXR (PXR protein/PXR mRNA ratio) was inversely correlated with the expression levels of miR-148a in a panel of 25 human livers, supporting the miR-148a-dependent regulation of PXR in human livers. Eventually, the PXR protein level was significantly correlated with the CYP3A4 mRNA and protein levels. In conclusion, we found that miR-148a post-transcriptionally regulated human PXR, resulting in the modulation of the inducible and/or constitutive levels of CYP3A4 in human liver. This study will provide new insight into the unsolved mechanism of the large interindividual variability of CYP3A4 expression. | |||||||
| 著者版フラグ | ||||||||
| 出版タイプ | AM | |||||||
| 出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||||
