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Hypothalamic cocaine-amphetamine regulated transcript (CART) is regulated by glucocorticoids |
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| Authors: | Vrang Niels Larsen Philip J Tang-Christensen Mads Larsen Leif Kongskov Kristensen Peter |
| Affiliation: | a Institute of Molecular Cardiobiology, The Johns Hopkins University, Baltimore, MD 21205, USA b Department of Surgery, The Johns Hopkins University, Baltimore, MD 21205, USA |
| 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 H2O2 in a concentration-dependent manner. These effects were abolished by 5-hydroxydecanoate (5HD; 500 μmol/l), a mitoKATP channel blocker. The present results showed that nicorandil has anti-apoptotic effects in neurons, at least in part, by preserving ΔΨm. |
| Keywords: | Mitochondria Potassium channel Oxidative stress Apoptosis Neuron |
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