論文 - 詳細
| RRC ID | 61735 |
|---|---|
| 著者 | Terada Y, Ogura J, Tsujimoto T, Kuwayama K, Koizumi T, Sasaki S, Maruyama H, Kobayashi M, Yamaguchi H, Iseki K. |
| タイトル | Intestinal P-glycoprotein expression is multimodally regulated by intestinal ischemia-reperfusion. |
| ジャーナル | J Pharm Pharm Sci |
| Abstract |
PURPOSE:Reactive oxygen species (ROS) have multiple physiological effects that are amount-dependent. ROS are one of the causes of intestinal ischemia-reperfusion (I/R) injury. In this study, we investigated whether the amount of ROS and the degree of intestinal I/R injury affect the expression level of P-glycoprotein (P-gp). METHODS:. We used hydrogen peroxide (H2O2) as ROS in in vitro experiments. Intestinal I/R model rats, which were subjected 15-min ischemia (I/R-15), were used in in vivo experiments. RESULTS:P-gp expression in Caco-2 cells was increased in response to 1 µM of H2O2 but decreased upon exposure to 10 mM of H2O2. We previously reported that P-gp expression is decreased after intestinal I/R with 30-min ischemia (I/R-30), which time a large amount of ROS is generated. I/R-15 induced slightly less mucosal and oxidative injury than did I/R-30. P-gp expression in the jejunum was increased at 1 h after I/R-15, and ileal paracellular permeability was increased. The blood concentration of tacrolimus, a P-gp substrate, was lower during 0-20 min but was higher during 40-90 min post-administration compared with that in the sham-operated rats. P-gp expression in the ileum was decreased at 6 h after I/R-15, due to abnormal localization of P-gp, resulting in a high blood tacrolimus concentration in rats reperfused for 6 h. CONCLUSIONS:ROS multimodally regulate P-gp expression depending on its amount. This is important for understanding the pattern of P-gp expression after intestinal I/R. |
| 巻・号 | 17(2) |
| ページ | 266-76 |
| 公開日 | 2014-1-1 |
| DOI | 10.18433/j3jg7d |
| PMID | 24934555 |
| MeSH | ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis* ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics Animals Caco-2 Cells Cells, Cultured Dose-Response Relationship, Drug Humans Hydrogen Peroxide / pharmacology Intestinal Mucosa / metabolism* Intestines / pathology* Male Rats Rats, Wistar Reactive Oxygen Species / metabolism Reperfusion Injury / genetics Reperfusion Injury / metabolism* Structure-Activity Relationship Tacrolimus / blood |
| IF | 1.667 |
| リソース情報 | |
| ヒト・動物細胞 | CACO-2(RCB0988) |