bcrp - publications

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1. J Pharm Pharm Sci. 2012 Jan;15(2):295-304.

Intestinal Ischemia-Reperfusion Increases Efflux for Uric Acid Via Paracellular
Route in the Intestine, but Decreases that Via Transcellular Route Mediated by

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.

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. This article is open to POST-PUBLICATION REVIEW. Registered readers
(see "For Readers") may comment by clicking on ABSTRACT on the issue's contents

PMID: 22579008 [PubMed - in process]