Nicorandil inhibits oxidative stress and amyloid-β precursor protein processing in SH-SY5Y cells overexpressing APPsw.
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-3β 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 Aβ1-42 levels in the medium. In addition, nicorandil increased the protein levels of p-Akt and p-GSK-3β 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).
Department of VIP, First Affiliated Hospital of Dalian Medical University No. 222 Zhongshan Road, Xigang District, Dalian, Liaoning 116011, China.
Jing-Jing
JJ
Kong
Department of VIP, First Affiliated Hospital of Dalian Medical University No. 222 Zhongshan Road, Xigang District, Dalian, Liaoning 116011, China.
Duo-Duo
DD
Zhang
Department of VIP, First Affiliated Hospital of Dalian Medical University No. 222 Zhongshan Road, Xigang District, Dalian, Liaoning 116011, China.
Pai
P
Li
Department of VIP, First Affiliated Hospital of Dalian Medical University No. 222 Zhongshan Road, Xigang District, Dalian, Liaoning 116011, China.
Chun-Yang
CY
Wei
Department of VIP, First Affiliated Hospital of Dalian Medical University No. 222 Zhongshan Road, Xigang District, Dalian, Liaoning 116011, China.
Hong-Jiu
HJ
Yu
Department of VIP, First Affiliated Hospital of Dalian Medical University No. 222 Zhongshan Road, Xigang District, Dalian, Liaoning 116011, China.
Hua
H
Zhang
Department of VIP, First Affiliated Hospital of Dalian Medical University No. 222 Zhongshan Road, Xigang District, Dalian, Liaoning 116011, China.
Wei
W
Zhang
Department of VIP, First Affiliated Hospital of Dalian Medical University No. 222 Zhongshan Road, Xigang District, Dalian, Liaoning 116011, China.
Yan-Fu
YF
Wang
Department of Neurology, First Affiliated Hospital of China Medical University No. 155 Nanjing North Street, Heping District, Shenyang, Liaoning 110001, China.
Yun-Peng
YP
Cao
APP processing; Alzheimer’s disease; Nicorandil; PI3K/Akt/GSK-3β; oxidative stress