論文 - 詳細
| RRC ID | 61459 |
|---|---|
| 著者 | Takano M, Naka R, Sasaki Y, Nishimoto S, Yumoto R. |
| タイトル | Effect of cigarette smoke extract on P-glycoprotein function in primary cultured and newly developed alveolar epithelial cells. |
| ジャーナル | Drug Metab Pharmacokinet |
| Abstract |
The effect of cigarette smoke extract (CSE) on P-glycoprotein (P-gp) function in the distal lung is unclear. In this study, we first examined the expression and function of P-gp and the effect of CSE in rat primary cultured alveolar epithelial cells. The expression of P-gp protein was observed in type I-like cells, but not in type II cells. In type I-like cells, rhodamine 123 (Rho123) accumulation was enhanced by various P-gp inhibitors such as verapamil and cyclosporine A. In addition, the expression of P-gp mRNAs, mdr1a and mdr1b, as well as P-gp activity increased along with the transdifferentiation. When type I-like cells were co-incubated with CSE, P-gp activity was suppressed. Next, we attempted to clarify the effect of CSE on P-gp function in human-derived cultured alveolar epithelial cells. For this purpose, we isolated an A549 clone (A549/P-gp) expressing P-gp, because P-gp expression in native A549 cells was negligible. In A549/P-gp cells, P-gp was functionally expressed, and the inhibitory effect of CSE on P-gp was observed. These results suggested that smoking would directly suppress P-gp activity, and that A549/P-gp cell line should be a useful model to further study the effect of xenobiotics on P-gp function in the alveolar epithelial cells. |
| 巻・号 | 31(6) |
| ページ | 417-424 |
| 公開日 | 2016-12-1 |
| DOI | 10.1016/j.dmpk.2016.08.006 |
| PII | S1347-4367(16)30067-2 |
| PMID | 27836711 |
| MeSH | A549 Cells ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism* Alveolar Epithelial Cells / cytology Alveolar Epithelial Cells / metabolism* Animals Cell Transdifferentiation Cells, Cultured Male RNA, Messenger / metabolism Rats, Sprague-Dawley Rhodamine 123 / analysis Tobacco Products* |
| IF | 2.772 |
| 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 | A549 |