Abstract
Purpose: :
Oxidative stress contributes to pathogenesis of glaucoma. Sirt1, NAD-dependent class IIIdeacetylase, functions in cellular senescence, cell survival, tumorigenesis, and life span. The purpose of this study has been to investigate whether sirt1 is concerned with oxidative stress and the novel effect of anti-glaucoma agent on the expression of sirt1 of trabecular meshwork (TM) cells.
Methods: :
The expression of sirt1 was investigated using two immortalized TM cell lines. Cells were treated with an anti-glaucoma drug and analyzed for the expression of sirt1, and cellular sensitivity to oxidative stress using Western blotting and WST-8 assay. Furthermore, the effect of an anti-glaucoma drug on the molecular regulation of the expression of sirt1 was examined using reporter assay and siRNA strategy.
Results: :
Glaucomatous TM cells highly expressed sirt1 when compared with normal TM cells. Knockdown of sirt1 expression significantly increased ROS level and rendered TM cells sensitive to hydrogen peroxide. Tafluprost induced the expression of sirt1 through the activation of c-myc transcription factor. Furthermore, TM cells reduced sensitivity to hydrogen peroxide when cells were treated with tafluprost.
Conclusions: :
These results indicate that sirt1 plays a critical role in prevention of oxidative stress in TM cells and tafluprost possesses a novel mechanism of action and function as potent protective agent against oxidative stress.
Keywords: trabecular meshwork • oxidation/oxidative or free radical damage • drug toxicity/drug effects