Nicorandil prevents oxidative stress-induced apoptosis in neurons by activating mitochondrial ATP-sensitive potassium channels

Yasushi Teshima, Masaharu Akao, William A. Baumgartner, Eduardo Marbán

Research output: Contribution to journalArticlepeer-review

Abstract

Nicorandil, a clinically useful drug for the treatment of ischemic heart disease, has an anti-apoptotic effect in cardiomyocytes, and activation of mitochondrial ATP-sensitive potassium (mitoKATP) channels underlies this effect. Recently, several studies showed that nicorandil reduced brain injury in animal models of brain ischemia. Based on these facts, we hypothesized that nicorandil may have anti-apoptotic effects in neurons mediated by mitoKATP channels. We investigated the effect of nicorandil on apoptosis induced by oxidative stress using cultured cerebellar granule neurons. Nicorandil (100 μmol/l) significantly suppressed the number of cells with TUNEL-positive nuclei and the increase in caspase-3 activity induced by 20 μmol/l H2O2. An indicator dye for mitochondrial inner membrane potential (ΔΨm) revealed that nicorandil prevented the loss of ΔΨm induced by H 2O2 in a concentration-dependent manner. These effects were abolished by 5-hydroxydecanoate (5HD; 500 μmol/l), a mitoK ATP channel blocker. The present results showed that nicorandil has anti-apoptotic effects in neurons, at least in part, by preserving ΔΨm.

Original languageEnglish (US)
Pages (from-to)45-50
Number of pages6
JournalBrain research
Volume990
Issue number1-2
DOIs
StatePublished - Nov 14 2003

Keywords

  • Apoptosis
  • Mitochondria
  • Neuron
  • Oxidative stress
  • Potassium channel

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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