title: Resveratrol protects PC12 cells from high glucose-induced neurotoxicity via PI3K/Akt/FoxO3a pathway.
abstract: Diabetes is known to be associated with neurodegenerative diseases. Resveratrol, a plant-derived polyphenolic compound found in red wine, possesses antioxidant properties. In this study, we aimed to investigate the effects of resveratrol on the phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt)/FoxO3a pathway in mediating high glucose (HG)-induced injuries in neuronal PC12 cells. PC12 cells were exposed to HG to establish a model of HG neurotoxicity. Results showed that pre-treating PC12 cells with resveratrol before exposure to HG led to increased cell viability, decreased apoptotic cells, and reactive oxygen species generation. Western blot analysis showed that HG decreased the phosphorylation of Akt and FoxO3a and led to the nuclear localization of FoxO3a. These effects were significantly alleviated by resveratrol co-treatment. Furthermore, the protective effects of resveratrol were abolished by PI3K/Akt inhibitor LY294002. All these results demonstrate that resveratrol protected the PC12 cells from HG-induced oxidative stress and apoptosis via the activation of PI3K/Akt/FoxO3a signaling pathway.
authors.affiliation: Department of Clinical Laboratory, Affiliated Nanhua Hospital, University of South China, No. 336 Dongfeng South Road, Hengyang, 421001, Hunan Province, People's Republic of China, mihualiu@163.com.
authors.forename: Mi-Hua
authors.initials: MH
authors.lastname: Liu
authors.forename: Cong
authors.initials: C
authors.lastname: Yuan
authors.forename: Jun
authors.initials: J
authors.lastname: He
authors.forename: Tian-Ping
authors.initials: TP
authors.lastname: Tan
authors.forename: Shao-Jian
authors.initials: SJ
authors.lastname: Wu
authors.forename: Hong-Yun
authors.initials: HY
authors.lastname: Fu
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Shan
authors.initials: S
authors.lastname: Yu
authors.forename: Yu-Dan
authors.initials: YD
authors.lastname: Chen
authors.forename: Qun-Fang
authors.initials: QF
authors.lastname: Le
authors.forename: Wei
authors.initials: W
authors.lastname: Tian
authors.forename: Heng-Jing
authors.initials: HJ
authors.lastname: Hu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Lin
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D005947:Glucose / Q000633:toxicity*; D008565:Membrane Proteins / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D000066829:Neuroprotection / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; C000606778:Bcl2l11 protein, rat; D002867:Chromones; C499515:FOXO3 protein, rat; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D008565:Membrane Proteins; D009025:Morpholines; D018696:Neuroprotective Agents; D009498:Neurotoxins; D011518:Proto-Oncogene Proteins; D017382:Reactive Oxygen Species; D013267:Stilbenes; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose; D000077185:Resveratrol; D000111:Acetylcysteine