TY - JOUR
T1 - Nipradilol inhibits apoptosis by preventing the activation of caspase-3 via S-nitrosylation and the cGMP-dependent pathway
AU - Tomita, Hiroshi
AU - Nakazawa, Toru
AU - Sugano, Eriko
AU - Abe, Toshiaki
AU - Tamai, Makoto
N1 - Funding Information:
This research was supported in part by the Kowa Company, Ltd. (Tokyo, Japan) and by a Grant-in-Aid for Scientific Research (no. 13771009) from the Ministry of Education of the Japanese Government.
PY - 2002/10/11
Y1 - 2002/10/11
N2 - To study whether nipradilol, which is used as an ophthalmic solution for the treatment of glaucoma, has a cytoprotective effect, we 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. We 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. We 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, we 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.
AB - To study whether nipradilol, which is used as an ophthalmic solution for the treatment of glaucoma, has a cytoprotective effect, we 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. We 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. We 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, we 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.
KW - Apoptosis
KW - Nipradilol
KW - Nitric oxide (NO)
KW - PC12 cell
KW - S-nitrosylation
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U2 - 10.1016/S0014-2999(02)02329-4
DO - 10.1016/S0014-2999(02)02329-4
M3 - Article
C2 - 12359266
AN - SCOPUS:0037064268
VL - 452
SP - 263
EP - 268
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 3
ER -