title: Quercetin Protects against Okadaic Acid-Induced Injury via MAPK and PI3K/Akt/GSK3β Signaling Pathways in HT22 Hippocampal Neurons.
abstract: Increasing evidence shows that oxidative stress and the hyperphosphorylation of tau protein play essential roles in the progression of Alzheimer's disease (AD). Quercetin is a major flavonoid that has anti-oxidant, anti-cancer and anti-inflammatory properties. We investigated the neuroprotective effects of quercetin to HT22 cells (a cell line from mouse hippocampal neurons). We found that Okadaic acid (OA) induced the hyperphosphorylation of tau protein at Ser199, Ser396, Thr205, and Thr231 and produced oxidative stress to the HT22 cells. The oxidative stress suppressed the cell viability and decreased the levels of lactate dehydrogenase (LDH), superoxide dismutase (SOD), mitochondria membrane potential (MMP) and Glutathione peroxidase (GSH-Px). It up-regulated malondialdehyde (MDA) production and intracellular reactive oxygen species (ROS). In addition, phosphoinositide 3 kinase/protein kinase B/Glycogen synthase kinase3β (PI3K/Akt/GSK3β) and mitogen activated protein kinase (MAPK) were also involved in this process. We found that pre-treatment with quercetin can inhibited OA-induced the hyperphosphorylation of tau protein and oxidative stress. Moreover, pre-treatment with quercetin not only inhibited OA-induced apoptosis via the reduction of Bax, and up-regulation of cleaved caspase 3, but also via the inhibition of PI3K/Akt/GSK3β, MAPKs and activation of NF-κB p65. Our findings suggest the therapeutic potential of quercetin to treat AD.
authors.affiliation: Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.|Department of Anatomy and Histoembryology, Zhaoqing Medical College, Zhaoqing, Guangdong, 526020, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Luo
authors.affiliation: Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.
authors.forename: Xiu-Yin
authors.initials: XY
authors.lastname: Shen
authors.affiliation: School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou, Guangdong, 510006, China.
authors.forename: Feng
authors.initials: F
authors.lastname: He
authors.affiliation: Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.
authors.forename: Hua-Qiao
authors.initials: HQ
authors.lastname: Wang
mesh_terms: D000818:Animals; D002460:Cell Line; D005979:Glutathione Peroxidase / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D020935:MAP Kinase Signaling System; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D019319:Okadaic Acid / Q000633:toxicity*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011794:Quercetin / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D016875:tau Proteins; D019319:Okadaic Acid; D011794:Quercetin; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D019869:Phosphatidylinositol 3-Kinases; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3