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

FEBS Letters

Guillouzo, André¹  Courtois, Arnaud¹  Fardel, Olivier¹  Payen, Léa¹ 

[1] INSERM U456 ‘Détoxication et Réparation Tissulaire’, Faculté de Pharmacie, 2 Avenue du Pr. L. Bernard, 35043 Rennes Cedex, France

关键词: Dexamethasone;    Hepatocyte;    Multidrug resistance-associated protein 2;    RU486;    Tyrosine aminotransferase;   

DOI  :  10.1016/S0014-5793(99)01295-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 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 anti-glucocorticoid 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.

【 授权许可】

Unknown