TY - JOUR
T1 - Decreased expression of P-glycoprotein during differentiation in the human intestinal cell line Caco-2
AU - Goto, Maki
AU - Masuda, Satohiro
AU - Saito, Hideyuki
AU - Inui, Ken Ichi
N1 - Funding Information:
We thank Dr. K. Ueda, Laboratory of Biochemistry, Division of Applied Life Sciences, Kyoto University Graduate School of Agriculture, for providing the MDR1 cDNA. This work was supported in part by a grant-in-aid from Japan Health Sciences Foundation, and by a grant-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2003/7/1
Y1 - 2003/7/1
N2 - The expression profile of the multidrug resistance (MDR) 1 gene product P-glycoprotein (Pgp) was examined during culture using Caco-2 cells as an in vitro model. Levels of MDR1 and cyclooxygenase 2 mRNA expression in Caco-2 cells were the highest on day 3 and decreased with days in culture, but the level of cyclooxygenase 1 was stable throughout the culture period. The stability of MDR1 mRNA was 7-fold higher on day 3 than on day 9, and the run-on assay suggested the transcription rate of the MDR1 gene on day 3 tended to be higher than on day 9. In addition, the expression of Pgp was comparable with that of MDR1 mRNA, but was inversely correlated with villin expression. The Pgp-mediated tacrolimus transport was the highest on day 1 and the lowest on day 11. These results suggested that the changeable mRNA stability rather than transcription rate of MDR1 contributed to its up-regulation during cell proliferation and down-regulation after post-confluent differentiation in Caco-2 cells. Therefore, the temporal induction and subsequent down-regulation of the enterocyte Pgp could affect bioavailability of several drugs during the regeneration of the intestinal wall.
AB - The expression profile of the multidrug resistance (MDR) 1 gene product P-glycoprotein (Pgp) was examined during culture using Caco-2 cells as an in vitro model. Levels of MDR1 and cyclooxygenase 2 mRNA expression in Caco-2 cells were the highest on day 3 and decreased with days in culture, but the level of cyclooxygenase 1 was stable throughout the culture period. The stability of MDR1 mRNA was 7-fold higher on day 3 than on day 9, and the run-on assay suggested the transcription rate of the MDR1 gene on day 3 tended to be higher than on day 9. In addition, the expression of Pgp was comparable with that of MDR1 mRNA, but was inversely correlated with villin expression. The Pgp-mediated tacrolimus transport was the highest on day 1 and the lowest on day 11. These results suggested that the changeable mRNA stability rather than transcription rate of MDR1 contributed to its up-regulation during cell proliferation and down-regulation after post-confluent differentiation in Caco-2 cells. Therefore, the temporal induction and subsequent down-regulation of the enterocyte Pgp could affect bioavailability of several drugs during the regeneration of the intestinal wall.
UR - http://www.scopus.com/inward/record.url?scp=0038343630&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0038343630&partnerID=8YFLogxK
U2 - 10.1016/S0006-2952(03)00242-9
DO - 10.1016/S0006-2952(03)00242-9
M3 - Article
C2 - 12818377
AN - SCOPUS:0038343630
SN - 0006-2952
VL - 66
SP - 163
EP - 170
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 1
ER -