Coordinate induction by antioxidants of UDP-glucuronosyltransferase UGT1A6 and the apical conjugate export pump MRP2 (multidrug resistance protein 2) in Caco-2 cells

被引:67
作者
Bock, KW
Eckle, T
Ouzzine, M
Fournel-Gigleux, S
机构
[1] Univ Tubingen, Inst Toxicol, D-72074 Tubingen, Germany
[2] Fac Med Vandoeuvre Nancy, UMR 7561, F-54505 Vandoeuvre Nancy, France
关键词
human UGT1A6; MRP2; cMOAT; Caco-2; cells; antioxidants;
D O I
10.1016/S0006-2952(99)00366-4
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Treatment of Caco-2 cells with the antioxidants quercetin or t-butylhydroquinone Led to induced protein levels of UDP-glucuronosyltransferase UGT1A6 (ca. 3-fold. over controls) and of the apical conjugate export pump multidrug resistance protein 2 (MRP2; 1.9-fold. ol-er controls). In contrast to UGT1A6, MRP2 (symbol ABCC2) was not inducible by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Immunocytochemistry demonstrated. that MRP2 was only expressed at the brush border domain of Caco-2 cell monolayers. The results indicate that UGT1A6 and MRP2 are coordinately induced by antioxidants, facilitating chemoprotection against phenolic toxins and excretion of conjugates into the intestinal lumen. (C) 2000 Elsevier Science Inc.
引用
收藏
页码:467 / 470
页数:4
相关论文
共 25 条
[1]   PARACETAMOL GLUCURONIDATION BY RECOMBINANT RAT AND HUMAN PHENOL UDP-GLUCURONOSYLTRANSFERASES [J].
BOCK, KW ;
FORSTER, A ;
GSCHAIDMEIER, H ;
BRUCK, M ;
MUNZEL, P ;
SCHARECK, W ;
FOURNELGIGLEUX, S ;
BURCHELL, B .
BIOCHEMICAL PHARMACOLOGY, 1993, 45 (09) :1809-1814
[2]   REGULATION AND EXPRESSION OF 4 CYTOCHROME-P-450 ISOENZYMES, NADPH-CYTOCHROME-P-450 REDUCTASE, THE GLUTATHIONE TRANSFERASE-B AND TRANSFERASE-C AND MICROSOMAL EPOXIDE HYDROLASE IN PRENEOPLASTIC AND NEOPLASTIC LESIONS IN RAT-LIVER [J].
BUCHMANN, A ;
KUHLMANN, W ;
SCHWARZ, M ;
KUNZ, W ;
WOLF, CR ;
MOLL, E ;
FRIEDBERG, T ;
OESCH, F .
CARCINOGENESIS, 1985, 6 (04) :513-521
[3]   EXPRESSION OF CYTOCHROME-P-450 3A IN HT29-MTX CELLS AND CACO-2 CLONE TC7 [J].
CARRIERE, V ;
LESUFFLEUR, T ;
BARBAT, A ;
ROUSSET, M ;
DUSSAULX, E ;
COSTET, P ;
DEWAZIERS, I ;
BEAUNE, P ;
ZWEIBAUM, A .
FEBS LETTERS, 1994, 355 (03) :247-250
[4]  
Cui YH, 1999, MOL PHARMACOL, V55, P929
[5]  
FOURNELGIGLEUX S, 1991, MOL PHARMACOL, V39, P177
[6]   FORMATION OF MONOGLUCURONIDES AND DIGLUCURONIDES AND OTHER GLYCOSIDES OF BENZO(A)PYRENE-3,6-QUINOL BY V79 CELL-EXPRESSED HUMAN PHENOL UDP-GLUCURONOSYLTRANSFERASES OF THE UGT1 GENE-COMPLEX [J].
GSCHAIDMEIER, H ;
SEIDEL, A ;
BURCHELL, B ;
BOCK, KW .
BIOCHEMICAL PHARMACOLOGY, 1995, 49 (11) :1601-1606
[7]  
Jedlitschky G, 1996, CANCER RES, V56, P988
[8]   ATP-dependent transport of bilirubin glucuronides by the multidrug resistance protein MRP1 and its hepatocyte canalicular isoform MRP2 [J].
Jedlitschky, G ;
Leier, I ;
Buchholtz, U ;
HummelEisenbeiss, J ;
Burchell, B ;
Keppler, D .
BIOCHEMICAL JOURNAL, 1997, 327 :305-310
[9]   THE GLUCURONIDATION OF HYDROXYLATED METABOLITES OF BENZO[A]PYRENE AND 2-ACETYLAMINOFLUORENE BY CDNA-EXPRESSED HUMAN UDP-GLUCURONOSYLTRANSFERASES [J].
JIN, CJ ;
MINERS, JO ;
BURCHELL, B ;
MACKENZIE, PI .
CARCINOGENESIS, 1993, 14 (12) :2637-2639
[10]   Expression and localization of the conjugate export pump encoded by the MRP2 (cMRP/cMOAT) gene in liver [J].
Keppler, D ;
Konig, J .
FASEB JOURNAL, 1997, 11 (07) :509-516