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JH Boatright, E Stodulkova, HT Nguyen, VT Do, JM Nickerson; The Effect of Retinoids and Butyrate on the Expression of CRX and IRBP in Retinoblastoma Cells . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3651.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To determine whether differentiation agents such as retinoids and butyrate regulate transcription of interphotoreceptor retinoid binding protein (IRBP) and Cone rod homeobox (CRX), a homeodomain transcription factor that may regulate IRBP promoter activity. Methods: WERI-Rb1 retinoblastoma cells were treated with various concentrations of all-trans retinol, all-trans retinoic acid, or butyrate during a 16 hour incubation. IRBP and CRX mRNA levels were determined by quantitative RT-PCR. GAPDH mRNA was used for normalization in every comparison. In other experiments, WERI cells were transfected with CAT reporter constructs containing various IRBP promoters. These cells were then treated with retinoic acid. Results: Butyrate at low concentrations increased mRNA levels but suppressed them at higher concentrations. Retinoic acid had minimal effects on either transcript. Additionally, retinoic acid had no effect on IRBP promoter activity. Conversely, retinol increased CRX mRNA over four fold. Conclusion: In WERI-Rb1 retinoblastoma cells, IRBP and CRX transcript levels are sensitive to butyrate. CRX expression is sensitive to retinol. To our knowledge, this is the first report of CRX expression being regulated by small affecter molecules. It is perhaps not surprising that retinol, a retinoid of central importance to the visual cycle, may affect the transcription of photo-responsive genes; such a regulatory mechanism might be expected to be unique to the photoreceptor cell.
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