Abstract
Abstract: :
Purpose: Nipradilol is an α1 ß blocker that is used as an antiglaucomatous agent and it has a cytoprotective effect in neuronal cells. Recently, it was reported that decrease of caspase–3 activity resulting in inhibition of apoptosis is implied in the mechanism of cytoprotection. However, whether nipradilol regulates gene expression is not known. We tried to clarify the effects of nipradilol on the expressions of apoptosis associated genes and the activation of NF–kappaB during serum deprivation–induced apoptosis in PC12 cells. Methods: PC12 cells were cultured in serum free RPMI1640 medium with 0.01, 0.1, 1, 10 µM or without nipradilol. Cells were cultured in medium with serum for controls. Gene expression of Bax, Bcl–2, Fas, FasL, Caspase–1, 2, 3 and 9, p53 and smac/DIABLO were examined by quantitative real time polymerase chain reaction. Translocation into nucleus of NF–kappaB was examined by electrophoresis mobility shift assay using NF–kappaB consensus sequenced DNA probe. Results: Gene expressions of Bax and capase–3 and 9 were upregulated during serum deprivention–induced apoptosis in PC12 cells compared to serum controls. 0.1 and 1 µM of nipradilol suppressed expression of Bax, capase–3 and 9 and smac/DIABLO gene. Expressions of the other genes examined in this experiment were not affected by nipradilol. Translocation into nucleus of NF–kappaB was increased by 0.1 and 1 µM of nipradilol. Conclusions: These data suggest that nipradilol could regulate the apoptosis associated gene expression and NF–kappaB activation during prevention of apoptosis.
Keywords: apoptosis/cell death • neuroprotection • nitric oxide