REGULATION BY DEXAMETHASONE OF P-GLYCOPROTEIN EXPRESSION IN CULTURED RAT HEPATOCYTES
REGULATION BY DEXAMETHASONE OF P-GLYCOPROTEIN EXPRESSION IN CULTURED RAT HEPATOCYTES
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DOI：
10.1016/0014-5793(93)80167-s
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发表时间：
1993-07-26
期刊：
影响因子：
3.5
通讯作者：
GUILLOUZO, A
中科院分区：
文献类型：
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作者：
FARDEL, O;LECUREUR, V;GUILLOUZO, A
我们已经研究了P-糖蛋白（P-gp）的表达和功能在培养的大鼠肝细胞响应地塞米松（DEX），这是已知的调节各种肝功能。北方印迹分析显示，与新鲜分离的肝细胞相比，培养的未处理肝细胞中P-gp mRNA水平较高，而DEX处理的肝细胞也显示出升高的P-gp水平，尽管较弱。同样，蛋白质印迹分析表明，在DEX的情况下，维持在肝细胞中的高水平的P-gp。使用mdr基因特异性探针使我们能够表明，DEX调节的P-gp诱导在培养的肝细胞主要涉及，如果不是专门的，mdr 1基因调控。多柔比星P-gp介导的外排分析显示，与DEX处理的细胞相比，DEX处理的肝细胞中的细胞内多柔比星蓄积较低，因此表明过表达的P-gp是功能性的。这些数据清楚地表明，DEX治疗强烈调节P-gp的表达，在原代大鼠肝细胞培养通过对mdr 1基因的特异性作用。
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 hepatocytes 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, mdr1 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 mdr1 gene.