title: Effects of nicorandil in neuroprotective activation of PI3K/AKT pathways in a cellular model of Alzheimer's disease.
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.
authors.affiliation: Department of Neurology, First Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Kong
authors.forename: Guiru
authors.initials: G
authors.lastname: Ren
authors.forename: Ning
authors.initials: N
authors.lastname: Jia
authors.forename: Yanfu
authors.initials: Y
authors.lastname: Wang
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Bingkun
authors.initials: B
authors.lastname: Chen
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Cao
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D015151:Immunoblotting; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020108:Nicorandil / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection
chemical_list: D016564:Amyloid beta-Protein Precursor; D018696:Neuroprotective Agents; D020108:Nicorandil; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt