Regulation by dexamethasone of P‐glycoprotein expression in cultured rat hepatocytes

FEBS Letters

Guillouzo, André¹  Lecureur, Valérie¹  Fardel, Olivier¹ 

[1] INSERM U 49, Unité de recherches Hépatologiques, Hôpital Pontchaillou, 35033 Rennes, France

关键词: P-Glycoprotein;    mdr gene;    Rat hepatocyte;    Dexamethasone;    Doxorubicin;    Primary culture;    DEX;    dexamethasone;    GAPDH;    glyceraldehyde phosphate dehydrogenase;    GST7-7: glutathione-S-transferase 7-7;    MDR;    multidrug resistance;    P-gp;    P-glycoprotein;   

DOI  :  10.1016/0014-5793(93)80167-S

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We have examined P-glycoprotein (P-gp) expression and function in cultured rat hepatocytes in response to dexamethasone (DEX), which is known to modulate various liver functions. Northern blot analyses revealed high levels of P-gp mRNAs in cultured untreated liver cells in comparison to those found in freshly isolated hepatocytes, while DEX-treated hepatoeytes also displayed elevated, although weaker, P-gp levels. Similarly, Western blotting analysis indicated high levels of P-gp in liver cells maintained in the absence of DEX. The use of mdr gene-specific probes allowed us to show that DEX-modulated P-gp induction in cultured hepatocytes involved mostly, if not specifically, mdrl gene regulation. Doxorubicin P-gp-mediated efflux analyses revealed lower intracellular doxorubicin accumulation in DEX-untreated liver cells than in DEX-treated cells, thus indicating that over-expressed P-gp was functional. These data clearly show that DEX treatment strongly modulates P-gp expression in primary rat hepatocyte cultures through a specific effect on the mdrl gene.

【 授权许可】

Unknown