Up-regulation of multidrug resistance-associated protein 2 (MRP2) expression in rat hepatocytes by dexamethasone

被引:92
作者
Courtois, A [1 ]
Payen, L [1 ]
Guillouzo, A [1 ]
Fardel, O [1 ]
机构
[1] Fac Pharm, INSERM Detoxicat & Reparat Tissulaire U456, F-35043 Rennes, France
关键词
dexamethasone; hepatocyte; multidrug resistance-associated protein 2; RU486; tyrosine aminotransferase;
D O I
10.1016/S0014-5793(99)01295-8
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Regulation of multidrug resistance-associated protein (MRP2) expression in response to dexamethasone (DEX) was analyzed using mainly primary rat hepatocytes, Enhanced levels of MRP2 mRNAs associated with increased amounts of a 190 kDa MRP2 were found in cultured DEX-treated hepatocytes; similarly, administration of DEX to rats (100 mg/kg, i.p.) led to a marked increase of hepatic amounts of MRP2 mRNAs, Maximal induction of MRP2 expression in DEX-treated primary hepatocytes was reached with 10(-5) M DEX, a concentration higher than that (10(-7) M) required for maximal up-regulation of tyrosine aminotransferase (TAT), a typical glucocorticoid receptor-regulated enzyme. In addition, the antiglucocorticoid compound RU486 failed to inhibit MRP2 induction caused by DEX whereas it fully blocked that of TAT, These findings therefore demonstrate that DEX is a potent inducer of MRP2 expression in rat hepatocytes through a mechanism that seems not to involve the classical glucocorticoid receptor pathway, (C) 1999 Federation of European Biochemical Societies.
引用
收藏
页码:381 / 385
页数:5
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