DHPA Protects SH-SY5Y Cells from Oxidative Stress-Induced Apoptosis via Mitochondria Apoptosis and the Keap1/Nrf2/HO-1 Signaling Pathway
Yunhui Cai,
Ran Xiao,
Yadan Zhang,
Diya Xu,
Ni Wang,
Mengze Han,
Yili Zhang,
Lin Zhang,
Wenhua Zhou
Affiliations
Yunhui Cai
Hunan Key Laboratory of Processed Food for Special Medical Purpose, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, School of Food Science and Engineering, Center South University of Forestry and Technology, Changsha 410004, China
Ran Xiao
Hunan Key Laboratory of Processed Food for Special Medical Purpose, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, School of Food Science and Engineering, Center South University of Forestry and Technology, Changsha 410004, China
Yadan Zhang
Hunan Key Laboratory of Processed Food for Special Medical Purpose, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, School of Food Science and Engineering, Center South University of Forestry and Technology, Changsha 410004, China
Diya Xu
Hunan Key Laboratory of Processed Food for Special Medical Purpose, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, School of Food Science and Engineering, Center South University of Forestry and Technology, Changsha 410004, China
Ni Wang
Hunan Key Laboratory of Processed Food for Special Medical Purpose, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, School of Food Science and Engineering, Center South University of Forestry and Technology, Changsha 410004, China
Mengze Han
Hunan Key Laboratory of Processed Food for Special Medical Purpose, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, School of Food Science and Engineering, Center South University of Forestry and Technology, Changsha 410004, China
Yili Zhang
Hunan Key Laboratory of Processed Food for Special Medical Purpose, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, School of Food Science and Engineering, Center South University of Forestry and Technology, Changsha 410004, China
Lin Zhang
Hunan Key Laboratory of Processed Food for Special Medical Purpose, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, School of Food Science and Engineering, Center South University of Forestry and Technology, Changsha 410004, China
Wenhua Zhou
Hunan Key Laboratory of Processed Food for Special Medical Purpose, Hunan Key Laboratory of Forestry Edible Resources Safety and Processing, School of Food Science and Engineering, Center South University of Forestry and Technology, Changsha 410004, China
Oxidative stress in the brain is highly related to the pathogenesis of Alzheimer’s disease (AD). It could be induced by the overproduction of reactive oxygen species (ROS), produced by the amyloid beta (Aβ) peptide and excess copper (Cu) in senile plaques and cellular species, such as ascorbic acid (AA) and O2. In this study, the protective effect of 5-hydroxy-7-(4′-hydroxy-3′-methoxyphenyl)-1-phenyl-3-heptanone (DHPA) on Aβ(1–42)/Cu2+/AA mixture-treated SH-SY5Y cells was investigated via in vitro and in silico studies. The results showed that DHPA could inhibit Aβ/Cu2+/AA-induced SH-SY5Y apoptosis, OH· production, intracellular ROS accumulation, and malondialdehyde (MDA) production. Further research demonstrated that DHPA could decrease the ratio of Bax/Bcl-2 and repress the increase of mitochondrial membrane potential (MMP) of SH-SY5Y cells, to further suppress the activation of caspase-3, and inhibit cell apoptosis. Meanwhile, DHPA could inhibit the Aβ/Cu2+/AA-induced phosphorylation of Erk1/2 and P38 in SH-SY5Y cells, and increase the expression of P-AKT. Furthermore, DHPA could bind to Keap1 to promote the separation of Nrf2 to Keap1 and activate the Keap1/Nrf2/HO-1 signaling pathway to increase the expression of heme oxygenase-1 (HO-1), quinone oxidoreductase-1 (NQO1), glutathione (GSH), and superoxide dismutase (SOD). Thus, our results demonstrated that DHPA could inhibit Aβ/Cu2+/AA-induced SH-SY5Y apoptosis via scavenging OH·, inhibit mitochondria apoptosis, and activate the Keap1/Nrf2/HO-1 signaling pathway.
