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RR Krishnamoorthy, G Prasanna, R Dauphin, C Hulet, C Kelly, T Yorio; Transcriptional Regulation Of The ETB Gene In Human Non-pigmented Ciliary Epithelial Cells . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3244.
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Purpose: Intravitreal injection of endothelin-1 (ET-1) has been shown in animal studies to reduce intraocular (IOP) pressure both by enhancing outflow mechanisms and reducing aqueous humor formation. Previous studies by our group showed that ET-1 acting through the ETB receptor could reduce ion transport activity (as measured by a 86Rb uptake assay) and thereby decrease aqueous humor production by the HNPE cells. In the present study we sought to determine if ET-1 alters the DNA binding activity of transcription factor AP-1, and thereby influence ETB receptor expression in HNPE cells. Methods:HNPE cells were treated for 24 hr with ET-1 (1, 10, and 100 nM) and nuclear extracts were isolated from these cells. Another set of HNPE cells were pretreated with either the ETA receptor antagonist, BQ 610 (1 µM) or the ETB receptor antagonist, BQ 788 (1 µM), before treatment with ET-1 (100 nM) for 24 hr. Electrophoretic mobility shift assays were carried out on the nuclear extracts using consensus oligos for transcription factor AP-1. Results:HNPE cells treated with 100 nM ET-1 showed a increase in the DNA binding activity of transcription factor AP-1. This increase in the DNA binding activity could be blocked by pretreatment of HNPE cells with both the ETA and ETB receptor antagonists. Conclusion:ET-1-induced increase in DNA binding activity of transcription factor AP-1, and an enhanced expression of the ETB receptor could contribute to ET-1's effects on aqueous humor formation in the HNPE cells.
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