Nipradilol inhibits apoptosis by preventing the activation of caspase-3 via S-nitrosylation and the cGMP-dependent pathway

Hiroshi Tomita, Toru Nakazawa, Eriko Sugano, Toshiaki Abe, Makoto Tamai

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)263-268
Number of pages6
JournalEuropean Journal of Pharmacology
Volume452
Issue number3
DOIs
Publication statusPublished - 2002 Oct 11

Keywords

  • Apoptosis
  • Nipradilol
  • Nitric oxide (NO)
  • PC12 cell
  • S-nitrosylation

ASJC Scopus subject areas

  • Pharmacology

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