TY - JOUR
T1 - Intestinal ischemia-reperfusion increases efflux for uric acid via paracellular route in the intestine, but decreases that via transcellular route mediated by BCRP
AU - Ogura, Jiro
AU - Kuwayama, Kaori
AU - Takaya, Atsushi
AU - Terada, Yusuke
AU - Tsujimoto, Takashi
AU - Koizumi, Takahiro
AU - Maruyama, Hajime
AU - Fujikawa, Asuka
AU - Takahashi, Natsuko
AU - Kobayashi, Masaki
AU - Itagaki, Shirou
AU - Hirano, Takeshi
AU - Yamaguchi, Hiroaki
AU - Iseki, Ken
PY - 2012/4/18
Y1 - 2012/4/18
N2 - 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.
AB - 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.
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U2 - 10.18433/j3w896
DO - 10.18433/j3w896
M3 - Article
C2 - 22579008
AN - SCOPUS:84860876716
VL - 15
SP - 295
EP - 304
JO - Journal of Pharmacy and Pharmaceutical Sciences
JF - Journal of Pharmacy and Pharmaceutical Sciences
SN - 1482-1826
IS - 2
ER -