Document Detail

Intestinal ischemia-reperfusion increases efflux for uric acid via paracellular route in the intestine, but decreases that via transcellular route mediated by BCRP.
MedLine Citation:
PMID:  22579008     Owner:  NLM     Status:  MEDLINE    
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.
Jiro Ogura; Kaori Kuwayama; Atsushi Takaya; Yusuke Terada; Takashi Tsujimoto; Takahiro Koizumi; Hajime Maruyama; Asuka Fujikawa; Natsuko Takahashi; Masaki Kobayashi; Shirou Itagaki; Takeshi Hirano; Hiroaki Yamaguchi; Ken Iseki
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Société canadienne des sciences pharmaceutiques     Volume:  15     ISSN:  1482-1826     ISO Abbreviation:  J Pharm Pharm Sci     Publication Date:  2012  
Date Detail:
Created Date:  2012-05-14     Completed Date:  2012-09-17     Revised Date:  2013-05-20    
Medline Journal Info:
Nlm Unique ID:  9807281     Medline TA:  J Pharm Pharm Sci     Country:  Canada    
Other Details:
Languages:  eng     Pagination:  295-304     Citation Subset:  IM    
Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo, Japan.
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MeSH Terms
ATP-Binding Cassette Transporters / antagonists & inhibitors,  metabolism*
Adenosine / analogs & derivatives,  pharmacology
Caco-2 Cells
Cell Survival / drug effects
Intestines / injuries,  metabolism*
Mitochondria / drug effects,  metabolism
Neoplasm Proteins / antagonists & inhibitors,  metabolism*
Rats, Wistar
Reperfusion Injury / metabolism*
Rotenone / pharmacology
Uncoupling Agents / pharmacology
Uric Acid / metabolism*
Reg. No./Substance:
0/3-(6-isobutyl-9-methoxy-1,4-dioxo-1,2,3,4,6,7,12,12a-octahydropyrazino(1',2'-1,6)pyrido(3,4-b)indol-3-yl)propionic acid tert-butyl ester; 0/ABCG2 protein, human; 0/Abcg2 protein, rat; 0/Neoplasm Proteins; 0/Uncoupling Agents; 58-61-7/Adenosine; 69-93-2/Uric Acid; 83-79-4/Rotenone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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