pgp - publications

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1. Invest Ophthalmol Vis Sci. 2012 May 8. [Epub ahead of print]

Expression and activity of p-glycoprotein elevated by dexamethasone in cultured
retinal pigment epithelium involve glucocorticoid receptor and pregnane X

Zhang Y, Lu M, Sun X, Li C, Kuang X, Ruan X.

Departments of Ophthalmology and Anesthesiology, First Municipal People's
Hospital of Guangzhou, Affiliated Hospital of Guangzhou Medical College,
Guangzhou, 510080, China.

Purpose: To investigate whether dexamethasone has an effect on functional
expression of p-glycoprotein in cultured human retinal pigment epithelium (RPE)
and, if so, whether this occurs through interaction with glucocorticoid receptor
(GR) and pregnane X receptor (PXR).Methods: The human RPE D407 was treated with
increasing concentrations of dexamethasone and/or RU486 for various time periods
up to 24 h. Treated cells were collected for cell viability, expressions of
p-glycoprotein and PXR, and rhodamine 123 accumulation assays. GR expression
plasmid and rifampicin were chosen to investigate the relationship of GR/PXR
activation and p-glycoprotein expression. Results: Significant increases in
p-glycoprotein as indicated by mRNA and protein levels as well as by functional
activity were induced within 12 h of dexamethasone treatment, persisted as long
as 24 h, and were dose-dependent and attenuable with coculture of RU486. In
parallel, a dose-dependent upregulation of PXR was notable at both mRNA and
protein levels by 24 h of dexamethasone treatment, and was partially reversible
with RU486 coculture. Additionally, transfection of GR expression plasmid
increased the transitional expressions of PXR and p-glycoprotein in untreated
cells, and enhanced PXR transcriptional expression in dexamethasone-treated
cells. Further, PXR silencing inhibited the dexamethasone-induced p-glycoprotein
alterations. However, rifampicin had no apparent effects on the
dexamethasone-induced p-glycoprotein alterations.Conclusion: Our results suggest
for the first time that expression and activation of p-glycoprotein involve GR
and PXR in human RPE.

PMID: 22570346 [PubMed - as supplied by publisher]