論文 - 詳細
RRC ID | 43838 |
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著者 | Ogura J, Kuwayama K, Takaya A, Terada Y, Tsujimoto T, Koizumi T, Maruyama H, Fujikawa A, Takahashi N, Kobayashi M, Itagaki S, Hirano T, Yamaguchi H, Iseki K. |
タイトル | Intestinal ischemia-reperfusion increases efflux for uric acid via paracellular route in the intestine, but decreases that via transcellular route mediated by BCRP. |
ジャーナル | J Pharm Pharm Sci |
Abstract |
PURPOSE:Uric acid is thought to be one of the most important antioxidants in human biological fluids. Intestinal ischemia-reperfusion (I/R) is an important factor associated with high rates of morbidity and mortality. Reactive oxygen species (ROS) are responsible for intestinal I/R injury. The aim of this study was to clarify the efflux for uric acid from the intestine after intestinal I/R. METHODS:We used intestinal ischemia-reperfusion (I/R) model rats. Serosal to mucosal flux for [¹⁴C]-uric acid was assessed by using Ussing-type diffusion chambers. BCRP/Bcrp expression was assessed by Western blot analysis. Caco-2 cells were used for a model of the intestinal epithelium, and rotenone was used as a mitochondrial dysfunction inducer. RESULTS:Serosal to mucosal flux for uric acid was increased after intestinal I/R, and that for mannitol was also increased. Ko143, which is a BCRP inhibitor, did not affect the uric acid transport. The decreasing uric acid transport mediated by Bcrp was caused by decrease in the level of Bcrp homodimer, bridged by an S-S bond. The suppression of Bcrp S-S bond formation was associated with mitochondrial dysfunction. Moreover, BCRP S-S bond formation activity was decreased by rotenone in Caco-2 cells. CONCLUSIONS:Serosal to mucosal flux for uric acid is significantly increased via the paracelluler route, but that via the transcellular route mediated by Bcrp is decreased after intestinal I/R. The decreasing uric acid flux mediated by Bcrp is caused by suppression of Bcrp S-S bond formation. This suppression of Bcrp S-S bond formation may be related to mitochondrial dysfunction. |
巻・号 | 15(2) |
ページ | 295-304 |
公開日 | 2012-1-1 |
DOI | 10.18433/j3w896 |
PMID | 22579008 |
MeSH | ATP Binding Cassette Transporter, Subfamily G, Member 2 ATP-Binding Cassette Transporters / antagonists & inhibitors ATP-Binding Cassette Transporters / metabolism* Adenosine / analogs & derivatives Adenosine / pharmacology Animals Caco-2 Cells Cell Survival / drug effects Diketopiperazines Heterocyclic Compounds, 4 or More Rings Humans Intestinal Mucosa / metabolism* Intestines / injuries Male Mitochondria / drug effects Mitochondria / metabolism Neoplasm Proteins / antagonists & inhibitors Neoplasm Proteins / metabolism* Rats Rats, Wistar Reperfusion Injury / metabolism* Rotenone / pharmacology Uncoupling Agents / pharmacology Uric Acid / metabolism* |
IF | 1.667 |
引用数 | 11 |
WOS 分野 | PHARMACOLOGY & PHARMACY |
リソース情報 | |
ヒト・動物細胞 | CACO-2(RCB0988) |