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Abstract #8330 Published in IGR 4-3
Nipradilol inhibits apoptosis by preventing the activation of caspase-3 via S-nitrosylation and the cGMP-dependent pathway
Tomita H; Nakazawa T; Sugano E; Abe T; Tamai MEuropean Journal of Pharmacology 2002; 452: 263-268
To study whether nipradilol, which is used as an ophthalmic solution for the treatment of glaucoma, has a cytoprotective effect, the authors investigated its effect on the apoptosis induced by serum withdrawal in PC12 cells. Nipradilol has α1- and β-adrenoceptor-blocking and nitric oxide (NO)-donating properties. They also investigated the effects of timolol, prazosin and S-nitroso-N-acetylpenicillamine (SNAP) on PC12 cell death. Serum withdrawal from PC12 cells resulted in apoptosis, and the survival rate was decreased in a time-dependent manner. The addition of nipradilol to the medium showed a cytoprotective effect on PC12 cell death in a dose-dependent manner, but timolol and prazosin did not. The authors measured caspase-3 activity to clarify the mechanism of the inhibition of apoptosis in the presence or absence of dithiothreitol (DTT). The caspase-3 activity could be reactivated by DTT. In addition, to investigate the relationship of the cGMP-dependent pathway to the nipradilol-induced cytoprotective effect, they tested the effect of the protein kinase G inhibitor KT5823. KT5823 partially reversed the nipradilol-mediated cytoprotective effect. These results indicate that the cytoprotective effect of nipradilol in PC12 cell death was due to the caspase-3 inhibition mediated by NO-related S-nitrosylation and activation of protein kinase G.
H. Tomita, MD, Department of Ophthalmology, Tohoku University School of Medicine, 1-1 Seiryo-machi, Sendai 980-8574, Japan. h-tomita@oph.med.tohoku.ac.jp
Classification:
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
