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FEBS Lett. 1993 Jul 26;327(2):189-93.

Regulation by dexamethasone of P-glycoprotein expression in cultured rat hepatocytes.

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1
INSERM U 49, Unité de recherches Hépatologiques, Hôpital Pontchaillou, Rennes, France.

Abstract

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.

PMID:
8101494
DOI:
10.1016/0014-5793(93)80167-s
[Indexed for MEDLINE]
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