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

Investigative Ophthalmology & Visual Science
Yuehong ZhangXiangcai Ruan

Abstract

To investigate whether dexamethasone has an effect on functional expression of p-glycoprotein in cultured human RPE and, if so, whether this occurs through interaction with glucocorticoid receptor (GR) and pregnane X receptor (PXR). The human RPE D407 was treated with increasing concentrations of dexamethasone and/or RU486 for various time periods up to 24 hours. 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. Significant increases in p-glycoprotein, as indicated by mRNA and protein levels, as well as by functional activity, were induced within 12 hours of dexamethasone treatment, persisted as long as 24 hours, 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 hours 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 transcription...Continue Reading

Citations

Jun 19, 2013·Trends in Pharmacological Sciences·Gary N Y ChanReina Bendayan
Sep 3, 2013·Biological & Pharmaceutical Bulletin·Takuro KoboriShogo Tokuyama
Dec 2, 2014·Pharmacology & Therapeutics·Renata SilvaFernando Remião
May 1, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Panpan LiVerena Prokosch

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