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Quercetin Protects against Okadaic Acid-Induced Injury via MAPK and PI3K/Akt/GSK3β Signaling Pathways in HT22 Hippocampal Neurons.
PLoS One. 2016; 11(4):e0152371.Plos

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+Show Affiliations

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.Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.School of Pharmaceutical Science, Sun Yat-sen University, Guangzhou, Guangdong, 510006, China.Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27050422

Citation

Jiang, Wei, et al. "Quercetin Protects Against Okadaic Acid-Induced Injury Via MAPK and PI3K/Akt/GSK3β Signaling Pathways in HT22 Hippocampal Neurons." PloS One, vol. 11, no. 4, 2016, pp. e0152371.
Jiang W, Luo T, Li S, et al. Quercetin Protects against Okadaic Acid-Induced Injury via MAPK and PI3K/Akt/GSK3β Signaling Pathways in HT22 Hippocampal Neurons. PLoS One. 2016;11(4):e0152371.
Jiang, W., Luo, T., Li, S., Zhou, Y., Shen, X. Y., He, F., Xu, J., & Wang, H. Q. (2016). Quercetin Protects against Okadaic Acid-Induced Injury via MAPK and PI3K/Akt/GSK3β Signaling Pathways in HT22 Hippocampal Neurons. PloS One, 11(4), e0152371. https://doi.org/10.1371/journal.pone.0152371
Jiang W, et al. Quercetin Protects Against Okadaic Acid-Induced Injury Via MAPK and PI3K/Akt/GSK3β Signaling Pathways in HT22 Hippocampal Neurons. PLoS One. 2016;11(4):e0152371. PubMed PMID: 27050422.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Quercetin Protects against Okadaic Acid-Induced Injury via MAPK and PI3K/Akt/GSK3β Signaling Pathways in HT22 Hippocampal Neurons. AU - Jiang,Wei, AU - Luo,Tao, AU - Li,Sheng, AU - Zhou,Yue, AU - Shen,Xiu-Yin, AU - He,Feng, AU - Xu,Jie, AU - Wang,Hua-Qiao, Y1 - 2016/04/06/ PY - 2015/12/06/received PY - 2016/03/14/accepted PY - 2016/4/7/entrez PY - 2016/4/7/pubmed PY - 2016/8/23/medline SP - e0152371 EP - e0152371 JF - PloS one JO - PLoS One VL - 11 IS - 4 N2 - 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/27050422/Quercetin_Protects_against_Okadaic_Acid_Induced_Injury_via_MAPK_and_PI3K/Akt/GSK3β_Signaling_Pathways_in_HT22_Hippocampal_Neurons_ L2 - https://dx.plos.org/10.1371/journal.pone.0152371 DB - PRIME DP - Unbound Medicine ER -