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Effects of Nicorandil in Neuroprotective Activation of PI3K/AKT Pathways in a Cellular Model of Alzheimer's Disease.
- Source :
-
European Neurology . Oct2013, Vol. 70 Issue 3/4, p233-241. 9p. 9 Graphs. - Publication Year :
- 2013
-
Abstract
- Nicorandil, an ATP-sensitive potassium (KATP) channel opener, is known to have protective effects on ischemic injury in heart and brain. One of the most important protective mechanisms is the anti-apoptotic effect on cardiomyocytes and neurons. This study explored the anti-apoptotic effect of nicorandil against neurotoxicity in SH-SY5Y cells overexpressing the Swedish mutant APP (APPsw) and the possible mechanisms involved. We used SH-SY5Y cells transiently transfected with APPsw as a cellular model of Alzheimer's disease. Cells were treated with nicorandil (0.1, 0.5, 1 mM) for 24 h with and without glibenclamide (10 μM), a KATP channel inhibitor. The cells were then collected for MTT, apoptosis assay, and Western blot. In addition, we also investigated the potential involvement of the PI3K/Akt pathway in nicorandil-mediated neuroprotection of APPsw cells. Our results showed that nicorandil dose-dependently increased cell viability and reduced the rate of apoptosis as measured by MTT assay and annexin V/PI staining. Western blot showed that nicorandil could upregulate Bcl-2 levels and downregulate Bax and caspase-3 expression. Further studies showed that nicorandil increased the levels of phospho-Akt and upregulated element-binding protein activity by PI3K activation. Applying a PI3K inhibitor, LY294002 blocked the protection. All these findings suggest that nicorandil might be a potential treatment option for Alzheimer's disease. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00143022
- Volume :
- 70
- Issue :
- 3/4
- Database :
- Academic Search Index
- Journal :
- European Neurology
- Publication Type :
- Academic Journal
- Accession number :
- 91660128
- Full Text :
- https://doi.org/10.1159/000351247