Nicorandil Inhibits Oxidative Stress And Amyloid-Beta Precursor Protein Processing In Sh-Sy5y Cells Overexpressing Appsw

It has been demonstrated that ATP-sensitive potassium (K-ATP) channel activation has neuroprotective effects against neuronal damage induced by hypoxia, ischemia or metabolism stress. This study investigated the multiply protective effects of K-ATP channel opener nicorandil against neurotoxicity in SH-SY5Y cells transiently transfected with Swedish mutant APP (APPsw) and also the potential involvement of PI3K/Akt/GSK-3 beta pathway. Cells were treated with nicorandil (1 mM) for 24 h with and without glibenclamide (10 mu M), a K-ATP channel inhibitor. Then the cells were collected for Hoechst33342, biochemical assays, real-time PCR, western blot and ELISA assay. Our results showed that nicorandil reduced apoptosis and decreased oxidative stress. Moreover, nicorandil down regulated APP695 mRNA and APP695 protein expression, also reduced A beta(1-42) levels in the medium. In addition, nicorandil increased the protein levels of p-Akt and p-GSK-3 beta by PI3K activation. Applying a PI3K inhibitor, LY294002 blocked the protection. These findings suggest nicorandil to be a potential therapeutic agent to treat Alzheimer's disease (AD).