Assuntos
Evolução Molecular , Farnesiltranstransferase/genética , Duplicação Gênica , Genoma de Planta , Proteínas de Plantas/genética , Solanaceae/genética , Motivos de Aminoácidos , Domínio Catalítico , Sequência Conservada , Farnesiltranstransferase/química , Expressão Gênica , Modelos Moleculares , Filogenia , Proteínas de Plantas/química , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Estrutura Secundária de Proteína , Seleção Genética , Alinhamento de Sequência , Solanaceae/classificaçãoRESUMO
It has been demonstrated that ATP-sensitive potassium (KATP) channel activation has neuroprotective effects against neuronal damage induced by hypoxia, ischemia or metabolism stress. This study investigated the multiply protective effects of KATP 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-3ß pathway. Cells were treated with nicorandil (1 mM) for 24 h with and without glibenclamide (10 µM), a KATP 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 Aß1-42 levels in the medium. In addition, nicorandil increased the protein levels of p-Akt and p-GSK-3ß 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).