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Abstract #23949 Published in IGR 11-2
Nipradilol and timolol induce Foxo3a and peroxiredoxin 2 expression and protect trabecular meshwork cells from oxidative stress
Miyamoto N; Izumi H; Miyamoto R; Kubota T; Tawara A; Sasaguri Y; Kohno KInvestigative Ophthalmology and Visual Science 2009; 50: 2777-2784
PURPOSE: Oxidative stress plays an important role in pathogenesis of glaucoma. The purpose of this study is to investigate the novel effect of antiglaucoma drugs on the expression of antioxidant peroxiredoxins of trabecular meshwork (TM) cells. METHODS: The expression of the peroxiredoxin family was investigated using immortalized TM cell lines. Cells were treated with antiglaucoma drugs and analyzed for the expression of peroxiredoxin, and cellular sensitivity to oxidative stress. Furthermore, the effect of antiglaucoma drugs on the molecular regulation of the expression of peroxiredoxin was examined using a reporter assay and siRNA strategy. RESULTS: Glaucomatous TM cells highly express peroxiredoxin 2 when compared with normal TM cells. Nipradilol and timolol, but not latanoprost, induce the expression of peroxiredoxin 2 through the activation of the Foxo3a transcription factor. TM cells showed reduced sensitivity to H(2)O(2) when cells were treated with either nipradilol or timolol, but not with latanoprost. In addition, both Foxo3a and PRDX2 expression were enhanced by drug-induced signal transduction through its receptor. CONCLUSIONS: These results indicate that both nipradilol and timolol possess a novel mechanism of action and function as potent protective agents against oxidative stress.
Department of Molecular Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan.
Classification:
2.5.1 Trabecular meshwork (Part of: 2 Anatomical structures in glaucoma > 2.5 Meshwork)
11.3.4 Betablocker (Part of: 11 Medical treatment > 11.3 Adrenergic drugs)